Graybiel AM


Full name : Graybiel Ann M

First name : Ann M

Mail : McGovern Institute of Brain Research, Massachusetts Institute of Technology

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References (62)

Title : Differential entrainment and learning-related dynamics of spike and local field potential activity in the sensorimotor and associative striatum - Thorn_2014_J.Neurosci_34_2845
Author(s) : Thorn CA , Graybiel AM
Ref : Journal of Neuroscience , 34 :2845 , 2014
Abstract : Parallel cortico-basal ganglia loops are thought to have distinct but interacting functions in motor learning and habit formation. In rats, the striatal projection neuron populations (MSNs) in the dorsolateral and dorsomedial striatum, respectively corresponding to sensorimotor and associative regions of the striatum, exhibit contrasting dynamics as rats acquire T-maze tasks (Thorn et al., 2010). Here, we asked whether these patterns could be related to the activity of local interneuron populations in the striatum and to the local field potential activity recorded simultaneously in the corresponding regions. We found that dorsolateral and dorsomedial striatal fast-spiking interneurons exhibited task-specific and training-related dynamics consistent with those of corresponding MSN populations. Moreover, both MSNs and interneuron populations in both regions became entrained to theta-band (5-12 Hz) frequencies during task acquisition. However, the predominant entrainment frequencies were different for the sensorimotor and associative zones. Dorsolateral striatal neurons became entrained mid-task to oscillations centered approximately 5 Hz, whereas simultaneously recorded neurons in the dorsomedial region became entrained to higher frequency ( approximately 10 Hz) rhythms. These region-specific patterns of entrainment evolved dynamically with the development of region-specific patterns of interneuron and MSN activity, indicating that, with learning, these two striatal regions can develop different frequency-modulated circuit activities in parallel. We suggest that such differential entrainment of sensorimotor and associative neuronal populations, acquired through learning, could be critical for coordinating information flow throughout each trans-striatal network while simultaneously enabling nearby components of the separate networks to operate independently.
ESTHER : Thorn_2014_J.Neurosci_34_2845
PubMedSearch : Thorn_2014_J.Neurosci_34_2845
PubMedID: 24553926

Title : Neurons in the ventral striatum exhibit cell-type-specific representations of outcome during learning - Atallah_2014_Neuron_82_1145
Author(s) : Atallah HE , McCool AD , Howe MW , Graybiel AM
Ref : Neuron , 82 :1145 , 2014
Abstract : The ventromedial striatum (VMS) is a node in circuits underpinning both affect and reinforcement learning. The cellular bases of these functions and especially their potential linkages have been unclear. VMS cholinergic interneurons, however, have been singled out as being related both to affect and to reinforcement-based conditioning, raising the possibility that unique aspects of their signaling could account for these functions. Here we show that VMS tonically active neurons (TANs), including putative cholinergic interneurons, generate unique bidirectional outcome responses during reward-based learning, reporting both positive (reward) and negative (reward omission) outcomes when behavioral change is prompted by switches in reinforcement contingencies. VMS output neurons (SPNs), by contrast, are nearly insensitive to switches in reinforcement contingencies, gradually losing outcome signaling while maintaining responses at trial initiation and goal approach. Thus, TANs and SPNs in the VMS provide distinct signals optimized for different aspects of the learning process.
ESTHER : Atallah_2014_Neuron_82_1145
PubMedSearch : Atallah_2014_Neuron_82_1145
PubMedID: 24908491

Title : Severe drug-induced repetitive behaviors and striatal overexpression of VAChT in ChAT-ChR2-EYFP BAC transgenic mice - Crittenden_2014_Front.Neural.Circuits_8_57
Author(s) : Crittenden JR , Lacey CJ , Lee T , Bowden HA , Graybiel AM
Ref : Front Neural Circuits , 8 :57 , 2014
Abstract : In drug users, drug-related cues alone can induce dopamine release in the dorsal striatum. Instructive cues activate inputs to the striatum from both dopaminergic and cholinergic neurons, which are thought to work together to support motor learning and motivated behaviors. Imbalances in these neuromodulatory influences can impair normal action selection and might thus contribute to pathologically repetitive and compulsive behaviors such as drug addiction. Dopamine and acetylcholine can have either antagonistic or synergistic effects on behavior, depending on the state of the animal and the receptor signaling systems at play. Semi-synchronized activation of cholinergic interneurons in the dorsal striatum drives dopamine release via presynaptic nicotinic acetylcholine receptors located on dopamine terminals. Nicotinic receptor blockade is known to diminish abnormal repetitive behaviors (stereotypies) induced by psychomotor stimulants. By contrast, blockade of postsynaptic acetylcholine muscarinic receptors in the dorsomedial striatum exacerbates drug-induced stereotypy, exemplifying how different acetylcholine receptors can also have opposing effects. Although acetylcholine release is known to be altered in animal models of drug addiction, predicting whether these changes will augment or diminish drug-induced behaviors thus remains a challenge. Here, we measured amphetamine-induced stereotypy in BAC transgenic mice that have been shown to overexpress the vesicular acetylcholine transporter (VAChT) with consequent increased acetylcholine release. We found that drug-induced stereotypies, consisting of confined sniffing and licking behaviors, were greatly increased in the transgenic mice relative to sibling controls, as was striatal VAChT protein. These findings suggest that VAChT-mediated increases in acetylcholine could be critical in exacerbating drug-induced stereotypic behaviors and promoting exaggerated behavioral fixity.
ESTHER : Crittenden_2014_Front.Neural.Circuits_8_57
PubMedSearch : Crittenden_2014_Front.Neural.Circuits_8_57
PubMedID: 24904300

Title : A feud that wasn't: acetylcholine evokes dopamine release in the striatum - Surmeier_2012_Neuron_75_1
Author(s) : Surmeier DJ , Graybiel AM
Ref : Neuron , 75 :1 , 2012
Abstract : In this issue of Neuron, Threlfell et al. (2012) report that synchronous activation of cholinergic interneurons evokes striatal dopamine release by activating presynaptic nicotinic acetylcholine receptors. These findings call for a fundamental reevaluation of the long-standing view that dopamine and acetylcholine "feud" over control of striatal circuitry.
ESTHER : Surmeier_2012_Neuron_75_1
PubMedSearch : Surmeier_2012_Neuron_75_1
PubMedID: 22794253

Title : Cell type-specific channelrhodopsin-2 transgenic mice for optogenetic dissection of neural circuitry function - Zhao_2011_Nat.Methods_8_745
Author(s) : Zhao S , Ting JT , Atallah HE , Qiu L , Tan J , Gloss B , Augustine GJ , Deisseroth K , Luo M , Graybiel AM , Feng G
Ref : Nat Methods , 8 :745 , 2011
Abstract : Optogenetic methods have emerged as powerful tools for dissecting neural circuit connectivity, function and dysfunction. We used a bacterial artificial chromosome (BAC) transgenic strategy to express the H134R variant of channelrhodopsin-2, ChR2(H134R), under the control of cell type-specific promoter elements. We performed an extensive functional characterization of the newly established VGAT-ChR2(H134R)-EYFP, ChAT-ChR2(H134R)-EYFP, Tph2-ChR2(H134R)-EYFP and Pvalb(H134R)-ChR2-EYFP BAC transgenic mouse lines and demonstrate the utility of these lines for precisely controlling action-potential firing of GABAergic, cholinergic, serotonergic and parvalbumin-expressing neuron subsets using blue light. This resource of cell type-specific ChR2(H134R) mouse lines will facilitate the precise mapping of neuronal connectivity and the dissection of the neural basis of behavior.
ESTHER : Zhao_2011_Nat.Methods_8_745
PubMedSearch : Zhao_2011_Nat.Methods_8_745
PubMedID: 21985008

Title : Shifting responsibly: the importance of striatal modularity to reinforcement learning in uncertain environments - Amemori_2011_Front.Hum.Neurosci_5_47
Author(s) : Amemori K , Gibb LG , Graybiel AM
Ref : Front Hum Neurosci , 5 :47 , 2011
Abstract : We propose here that the modular organization of the striatum reflects a context-sensitive modular learning architecture in which clustered striosome-matrisome domains participate in modular reinforcement learning (RL). Based on anatomical and physiological evidence, it has been suggested that the modular organization of the striatum could represent a learning architecture. There is not, however, a coherent view of how such a learning architecture could relate to the organization of striatal outputs into the direct and indirect pathways of the basal ganglia, nor a clear formulation of how such a modular architecture relates to the RL functions attributed to the striatum. Here, we hypothesize that striosome-matrisome modules not only learn to bias behavior toward specific actions, as in standard RL, but also learn to assess their own relevance to the environmental context and modulate their own learning and activity on this basis. We further hypothesize that the contextual relevance or "responsibility" of modules is determined by errors in predictions of environmental features and that such responsibility is assigned by striosomes and conveyed to matrisomes via local circuit interneurons. To examine these hypotheses and to identify the general requirements for realizing this architecture in the nervous system, we developed a simple modular RL model. We then constructed a network model of basal ganglia circuitry that includes these modules and the direct and indirect pathways. Based on simple assumptions, this model suggests that while the direct pathway may promote actions based on striatal action values, the indirect pathway may act as a gating network that facilitates or suppresses behavioral modules on the basis of striatal responsibility signals. Our modeling functionally unites the modular compartmental organization of the striatum with the direct-indirect pathway divisions of the basal ganglia, a step that we suggest will have important clinical implications.
ESTHER : Amemori_2011_Front.Hum.Neurosci_5_47
PubMedSearch : Amemori_2011_Front.Hum.Neurosci_5_47
PubMedID: 21660099

Title : Differential dynamics of activity changes in dorsolateral and dorsomedial striatal loops during learning - Thorn_2010_Neuron_66_781
Author(s) : Thorn CA , Atallah H , Howe M , Graybiel AM
Ref : Neuron , 66 :781 , 2010
Abstract : The basal ganglia are implicated in a remarkable range of functions influencing emotion and cognition as well as motor behavior. Current models of basal ganglia function hypothesize that parallel limbic, associative, and motor cortico-basal ganglia loops contribute to this diverse set of functions, but little is yet known about how these loops operate and how their activities evolve during learning. To address these issues, we recorded simultaneously in sensorimotor and associative regions of the striatum as rats learned different versions of a conditional T-maze task. We found highly contrasting patterns of activity in these regions during task performance and found that these different patterns of structured activity developed concurrently, but with sharply different dynamics. Based on the region-specific dynamics of these patterns across learning, we suggest a working model whereby dorsomedial associative loops can modulate the access of dorsolateral sensorimotor loops to the control of action.
ESTHER : Thorn_2010_Neuron_66_781
PubMedSearch : Thorn_2010_Neuron_66_781
PubMedID: 20547134

Title : Pausing to regroup: thalamic gating of cortico-basal ganglia networks - Thorn_2010_Neuron_67_175
Author(s) : Thorn CA , Graybiel AM
Ref : Neuron , 67 :175 , 2010
Abstract : How the cholinergic and dopaminergic systems of the striatum interact and how these interface with the massive neocortical input to the striatum are classic questions of cardinal interest to neurology and psychiatry. In this issue of Neuron, Ding and colleagues show that a key to these puzzles lies in the thalamic inputs to the striatum targeting its cholinergic interneurons.
ESTHER : Thorn_2010_Neuron_67_175
PubMedSearch : Thorn_2010_Neuron_67_175
PubMedID: 20670826

Title : Dynamic cross-frequency couplings of local field potential oscillations in rat striatum and hippocampus during performance of a T-maze task - Tort_2008_Proc.Natl.Acad.Sci.U.S.A_105_20517
Author(s) : Tort AB , Kramer MA , Thorn CA , Gibson DJ , Kubota Y , Graybiel AM , Kopell NJ
Ref : Proc Natl Acad Sci U S A , 105 :20517 , 2008
Abstract : Oscillatory rhythms in different frequency ranges mark different behavioral states and are thought to provide distinct temporal windows that coherently bind cooperating neuronal assemblies. However, the rhythms in different bands can also interact with each other, suggesting the possibility of higher-order representations of brain states by such rhythmic activity. To explore this possibility, we analyzed local field potential oscillations recorded simultaneously from the striatum and the hippocampus. As rats performed a task requiring active navigation and decision making, the amplitudes of multiple high-frequency oscillations were dynamically modulated in task-dependent patterns by the phase of cooccurring theta-band oscillations both within and across these structures, particularly during decision-making behavioral epochs. Moreover, the modulation patterns uncovered distinctions among both high- and low-frequency subbands. Cross-frequency coupling of multiple neuronal rhythms could be a general mechanism used by the brain to perform network-level dynamical computations underlying voluntary behavior.
ESTHER : Tort_2008_Proc.Natl.Acad.Sci.U.S.A_105_20517
PubMedSearch : Tort_2008_Proc.Natl.Acad.Sci.U.S.A_105_20517
PubMedID: 19074268

Title : Learning-related coordination of striatal and hippocampal theta rhythms during acquisition of a procedural maze task - DeCoteau_2007_Proc.Natl.Acad.Sci.U.S.A_104_5644
Author(s) : DeCoteau WE , Thorn CA , Gibson DJ , Courtemanche R , Mitra P , Kubota Y , Graybiel AM
Ref : Proc Natl Acad Sci U S A , 104 :5644 , 2007
Abstract : The striatum and hippocampus are conventionally viewed as complementary learning and memory systems, with the hippocampus specialized for fact-based episodic memory and the striatum for procedural learning and memory. Here we directly tested whether these two systems exhibit independent or coordinated activity patterns during procedural learning. We trained rats on a conditional T-maze task requiring navigational and cue-based associative learning. We recorded local field potential (LFP) activity with tetrodes chronically implanted in the caudoputamen and the CA1 field of the dorsal hippocampus during 6-25 days of training. We show that simultaneously recorded striatal and hippocampal theta rhythms are modulated differently as the rats learned to perform the T-maze task but nevertheless become highly coherent during the choice period of the maze runs in rats that successfully learned the task. Moreover, in the rats that acquired the task, the phase of the striatal-hippocampal theta coherence was modified toward a consistent antiphase relationship, and these changes occurred in proportion to the levels of learning achieved. We suggest that rhythmic oscillations, including theta-band activity, could influence not only neural processing in cortico-basal ganglia circuits but also dynamic interactions between basal ganglia-based and hippocampus-based forebrain circuits during the acquisition and performance of learned behaviors. Experience-dependent changes in coordination of oscillatory activity across brain structures thus may parallel the well known plasticity of spike activity that occurs as a function of experience.
ESTHER : DeCoteau_2007_Proc.Natl.Acad.Sci.U.S.A_104_5644
PubMedSearch : DeCoteau_2007_Proc.Natl.Acad.Sci.U.S.A_104_5644
PubMedID: 17372196

Title : Oscillations of local field potentials in the rat dorsal striatum during spontaneous and instructed behaviors - DeCoteau_2007_J.Neurophysiol_97_3800
Author(s) : DeCoteau WE , Thorn CA , Gibson DJ , Courtemanche R , Mitra P , Kubota Y , Graybiel AM
Ref : Journal of Neurophysiology , 97 :3800 , 2007
Abstract : Oscillatory activity is a candidate mechanism for providing frequency coding for the generation, storage and replay of sequential representations of events and episodes. We recorded local field potentials (LFPs) and spike activity in the striatum, a basal ganglia structure implicated in behavioral action-sequence learning and performance, as rats engaged in spontaneous and instructed behaviors in a T-maze task. We found that during voluntary behaviors, striatal LFPs exhibit prominent theta-band oscillations together with rhythms at higher and lower frequencies. Analysis of the theta-band activity demonstrated that these oscillations are strongly modulated during task performance and increase as the animals choose and execute their turning responses in the cue-instructed T-maze task. These theta rhythms are locally generated and are coherent across large parts of the striatum. We suggest that modulation of oscillatory activity in the striatum may be a key feature of neural processing related to the control of voluntary behavior.
ESTHER : DeCoteau_2007_J.Neurophysiol_97_3800
PubMedSearch : DeCoteau_2007_J.Neurophysiol_97_3800
PubMedID: 17329629

Title : Local circuit neurons in the striatum regulate neural and behavioral responses to dopaminergic stimulation - Saka_2002_Proc.Natl.Acad.Sci.U.S.A_99_9004
Author(s) : Saka E , Iadarola M , Fitzgerald DJ , Graybiel AM
Ref : Proc Natl Acad Sci U S A , 99 :9004 , 2002
Abstract : Interneurons are critical for shaping neuronal circuit activity in many parts of the central nervous system. To study interneuron function in the basal ganglia, we tested and characterized an NK-1 receptor-based method for targeted ablation of specific classes of interneuron in the striatum. Our findings demonstrate that the neurotoxin SP-PE35, a substance P-Pseudomonas exotoxin conjugate, selectively targets striatal cholinergic and nitric oxide synthase/somatostatinergic interneurons when injected locally into the striatum. The effects of this selective cell targeting encompassed alterations in both behavioral and neural responses to dopaminergic stimulation, including altered patterns of early-gene response in striosomes and matrix. We conclude that NK-1-bearing local circuit neurons of the striatum regulate the differential responses of striatal projection neurons to dopamine-mediated signaling.
ESTHER : Saka_2002_Proc.Natl.Acad.Sci.U.S.A_99_9004
PubMedSearch : Saka_2002_Proc.Natl.Acad.Sci.U.S.A_99_9004
PubMedID: 12060713

Title : Neural networks: neural systems V: basal ganglia -
Author(s) : Graybiel AM
Ref : Am J Psychiatry , 158 :21 , 2001
PubMedID: 11136627

Title : Evidence for a deficit in cholinergic interneurons in the striatum in schizophrenia - Holt_1999_Neurosci_94_21
Author(s) : Holt DJ , Herman MM , Hyde TM , Kleinman JE , Sinton CM , German DC , Hersh LB , Graybiel AM , Saper CB
Ref : Neuroscience , 94 :21 , 1999
Abstract : Neurochemical and functional abnormalities of the striatum have been reported in schizophrenic brains, but the cellular substrates of these changes are not known. We hypothesized that schizophrenia may involve an abnormality in one of the key modulators of striatal output, the cholinergic interneuron. We measured the densities of cholinergic neurons in the striatum in schizophrenic and control brains in a blind analysis, using as a marker of this cell population immunoreactivity for choline acetyltransferase, the synthetic enzyme of acetylcholine. As an independent marker, we used immunoreactivity for calretinin, a protein which is co-localized with choline acetyltransferase in virtually all of the cholinergic interneurons of the striatum. A significant decrease in choline acetyltransferase-positive and calretinin-positive cell densities was found in the schizophrenic cases compared with controls in the striatum as a whole [for the choline acetyltransferase-positive cells: controls: 3.21 +/- 0.48 cells/mm2 (mean +/- S.D.), schizophrenics: 2.43 +/- 0.68 cells(mm2; P < 0.02]. The decrease was patchy in nature and most prominent in the ventral striatum (for the choline acetyltransferase-positive cells: controls: 3.47 +/- 0.59 cells/mm2, schizophrenics: 2.52 +/- 0.64 cells/ mm2; P < 0.005) which included the ventral caudate nucleus and nucleus accumbens region. Three of the schizophrenic cases with the lowest densities of cholinergic neurons had not been treated with neuroleptics for periods from more than a month to more than 20 years. A decrease in the number or function of the cholinergic interneurons of the striatum may disrupt activity in the ventral striatal-pallidal-thalamic-prefrontal cortex pathway and thereby contribute to abnormalities in function of the prefrontal cortex in schizophrenia.
ESTHER : Holt_1999_Neurosci_94_21
PubMedSearch : Holt_1999_Neurosci_94_21
PubMedID: 10613493

Title : Pattern formation in the developing superior colliculus: ontogeny of the periodic architecture in the intermediate layers - Illing_1994_J.Comp.Neurol_340_311
Author(s) : Illing RB , Graybiel AM
Ref : Journal of Comparative Neurology , 340 :311 , 1994
Abstract : The superior colliculus of mammals contains a striking neurochemical architecture in which histochemically identifiable compartments are distributed in an iterative arrangement in the intermediate layers. We used stains for acetylcholinesterase activity as a compartment marker to trace ontogenesis of this architecture during pre- and postnatal development in the domestic cat. We found that compartmentation in the intermediate collicular layers is virtually absent at birth, and only gradually emerges during the first weeks of postnatal life. Over the same postnatal period, acetylcholinesterase activity shifts from a predominantly perikaryal expression pattern immediately postnatally to a nearly exclusive localization in the neuropil at maturity. Remarkably, a striking compartmentation of the superior colliculus was readily apparent with acetylcholinesterase histochemistry prenatally. The first appearance of a periodic architecture in the superior colliculus was observed at embryonic day 34, a time at which the collicular plate had not yet become laminated. The compartments characterized by high levels of acetylcholinesterase activity then gained in prominence until late in the prenatal period, when they receded and disappeared. The loss of the acetylcholinesterase-positive compartments in the perinatal period did not reflect a loss of compartmentation altogether. Neonatally, there was a distinct compartmental architecture visible with enkephalin immunohistochemistry. The virtual absence of acetylcholinesterase-positive compartments in the superior colliculus at birth therefore reflects developmental regulation of enzyme expression in the compartments, not regulation of the compartments as structural entities. We conclude that the periodic architecture, which characterizes the intermediate collicular layers in the adult cat, arises early in ontogenesis. These observations raise the possibility that the histochemical compartments are ontogenetic units that undergo remodeling as the superior colliculus matures.
ESTHER : Illing_1994_J.Comp.Neurol_340_311
PubMedSearch : Illing_1994_J.Comp.Neurol_340_311
PubMedID: 8188853

Title : Enkephalin-positive and acetylcholinesterase-positive patch systems in the superior colliculus have matching distributions but distinct developmental histories - Graybiel_1994_J.Comp.Neurol_340_297
Author(s) : Graybiel AM , Illing RB
Ref : Journal of Comparative Neurology , 340 :297 , 1994
Abstract : Histochemical stains for acetylcholinesterase activity and enkephalin-like immunoreactivity both demonstrate a high degree of patterning in the superior colliculus, particularly in the intermediate and deep layers. Both markers occur predominantly in the neuropil of these layers, and both are principally distributed in distinct macroscopic compartments. We report here that patches of heightened acetylcholinesterase activity correspond to patches of high enkephalin-like immunoreactivity. The two markers thus delineate largely the same domain in the intermediate and deep layers. The most prominent zones of staining for enkephalin-like peptide and for acetylcholinesterase also coincided in the dorsolateral periaqueductal gray matter. These findings suggest a close interlocking of one or more acetylcholinesterase-containing systems with one or more pathways related to endogenous opioids in the superior colliculus. As the acetylcholinesterase expression in the patches is known to match in detail choline acetyltransferase expression, our results also suggest the possibility of local cholinergic-opiatergic interactions. In some sections, blood vessels associated with enkephalin-rich and acetylcholinesterase-rich patches extended beyond the colliculus into the periaqueductal gray matter, where they again became surrounded by dense fibrous labeling. This pattern suggests that neurohumoral signal exchange might occur through blood vessels even in a sensory-motor structure such as the colliculus. In a postnatal developmental series of kitten brains we found that enkephalin-like immunoreactivity was already distinctly compartmental in the intermediate layers at birth and continued to show this distribution throughout postnatal development. By contrast, acetylcholinesterase staining was nearly homogeneous at birth and became compartmental gradually during the first postnatal weeks. Thus, despite the eventual near coincidence of the enkephalin-rich and acetylcholinesterase-rich compartments of the superior colliculus, they mark systems that follow distinct programs of neurochemical development.
ESTHER : Graybiel_1994_J.Comp.Neurol_340_297
PubMedSearch : Graybiel_1994_J.Comp.Neurol_340_297
PubMedID: 8188852

Title : Influence of mesostriatal afferents on the development and transmitter regulation of intrastriatal grafts derived from embryonic striatal primordia - Liu_1992_J.Neurosci_12_4281
Author(s) : Liu FC , Dunnett SB , Graybiel AM
Ref : Journal of Neuroscience , 12 :4281 , 1992
Abstract : Embryonic striatal grafts develop a modular organization in which patches of tissue enriched in many transmitter substances characteristic of striatum (P regions) are embedded in surrounds (NP regions) expressing only low levels of these substances. Catecholaminergic fibers from the host brain, identified by their expression of tyrosine hydroxylase (TH), grow into such grafts and selectively terminate in the striatum-like P regions. This terminal pattern suggests that cell-cell affinities between neurons of the substantia nigra and striatum may play a role either in the aggregation of the striatal cells into P regions, or in the targeting of the TH-positive fibers to the cell clusters. In the present study, we tested the first of these possibilities. Striatal grafts derived from embryonic day 15 striatal primordia were implanted into the ibotenate-damaged host striatum of rats previously treated with 6-hydroxydopamine (6-OHDA) to destroy TH-containing dopaminergic nigrostriatal afferents. The 6-OHDA lesions that eliminated nearly all TH-like immunostaining in the host striatum also resulted in disappearance of nearly all TH-positive fibers in the grafts. In this dopamine-depleted environment, the grafts nevertheless developed a clear modular organization. They contained striatum-like patches with neurons expressing many of the neurochemicals characteristic of striatum (ACh, ChAT, calbindin-D28KD, met-enkephalin, and dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein-32,000 or DARPP-32), and these patches were surrounded by graft tissue expressing few of these striatal markers. These observations suggest that the ingrowth of TH-positive fibers from the host is not obligatory for the sorting out of striatal from nonstriatal cells during the formation of P regions in embryonic striatal grafts. Despite the fact that dopaminergic denervation of the host striatum did not disrupt either the aggregation of grafted cells into P regions or the acquisition of striatal neurochemical phenotypes by cells in the P regions, there were clear differences between the staining patterns of these grafts and grafts placed into dopamine-innervated striatum. Most striking was a sharp increase of met-enkephalin-like immunostaining in the P zones of the denervated grafts. Upregulation of met-enkephalin is known to occur in the dopamine-depleted mature striatum, and was observed in the parts of host striatum surrounding the grafts on the side ipsilateral to the 6-OHDA lesions. This result suggests that functional interactions between dopaminergic and enkephalinergic systems can occur in the striatal circuits reconstructed by embryonic striatal grafting. More generally, our results suggest that TH-containing afferents from the host striatum, though not required for induction and maintenance of striatal phenotypy in striatal grafts, can chronically regulate neurotransmitter/neuromodulator expression in neurons of the striatum-like P zones in a manner similar to that found for the normal striatum.
ESTHER : Liu_1992_J.Neurosci_12_4281
PubMedSearch : Liu_1992_J.Neurosci_12_4281
PubMedID: 1279138

Title : Compartmental organization of the thalamostriatal connection in the cat - Ragsdale_1991_J.Comp.Neurol_311_134
Author(s) : Ragsdale CW, Jr. , Graybiel AM
Ref : Journal of Comparative Neurology , 311 :134 , 1991
Abstract : The compartmental organization of the thalamostriatal connection in the cat was studied by labelling thalamic fibers in anterograde axonal transport experiments and comparing their striatal distributions with the arrangement of striosomes and matrix tissue identified by histochemical staining methods. When analyzed according to their principal compartmental targets in dorsal striatum, the thalamic deposits indicated the existence of medial and lateral divisions within the thalamostriatal projection. Nuclei of the medial division, which includes parts of the thalamic midline, projected primarily to striosomes. The lateral division, which embraces the anterior and posterior intralaminar groups, the rostral ventral tier nuclei, and parts of the posterior lateral nuclear complex, predominantly innervated matrix tissue. In the dorsal division of the nucleus accumbens, the medial system preferentially terminated in zones that stain heavily in butyrylcholinesterase and substance P preparations, but fibers from both the medial and the lateral systems largely avoided the histochemically marked compartments such as the border islands of the nucleus accumbens that are seen elsewhere in the ventral striatum. Medial division: Thalamic deposits involving the paraventricular and rhomboid nuclei of the thalamic midline elicited labelling of striosomes and, invariably, ventral extrastriosomal matrix, the nucleus accumbens, and the amygdala. This projection was topographically organized: rostral thalamic deposits elicited labelling in the medial caudate nucleus and the medial nucleus accumbens. More caudal injections produced more lateral labelling. Lateral division: The lateral division is composed of at least three projection systems distinguished by their patterns of matrix innervation. Deposits involving the anterior intralaminar nuclei and the striatally projecting cells located lateral to the stria medullaris (anterior intralaminar complex) produced an even, diffuse labelling of the matrix tissue and weak labelling of the striosomes. Injections placed in the ventroanterior, ventrolateral, and ventromedial nuclei (rostral ventral complex) elicited fibrous labelling of matrix tissue that often showed nonstriosomal inhomogeneities. Deposits involving the centromedian and parafascicular nuclei (posterior intralaminar complex) produced a highly variable pattern of matrix labelling that included both homogeneous and decidedly patchy innervations of the extrastriosomal matrix. Each of these lateral thalamostriatal systems showed a similar spatial organization, whereby dorsoventral and mediolateral thalamic axes were roughly preserved in the projection to striatum.
ESTHER : Ragsdale_1991_J.Comp.Neurol_311_134
PubMedSearch : Ragsdale_1991_J.Comp.Neurol_311_134
PubMedID: 1719043

Title : The substantia nigra and its relations with the striatum in the monkey -
Author(s) : Langer LF , Jimenez-Castellanos J , Graybiel AM
Ref : Prog Brain Res , 87 :81 , 1991
PubMedID: 1678193

Title : Tectorecipient zone of cat lateral posterior nucleus: evidence that collicular afferents contain acetylcholinesterase - Berson_1991_Exp.Brain.Res_84_478
Author(s) : Berson DM , Graybiel AM
Ref : Experimental Brain Research , 84 :478 , 1991
Abstract : The superficial layers of the cat's superior colliculus innervate the medial subdivision of the thalamic lateral posterior nucleus (LPm). LPm is set off from adjoining thalamic zones by its denser staining for acetyl-cholinesterase (AChE). We sought to learn whether the tectal afferents to LPm might themselves be the source of the enzyme staining by examining the effects of collicular lesions on the thalamic staining pattern. Large excitotoxin lesions of the colliculus largely eliminated AChE staining in the ipsilateral LPm. By contrast, fibersparing lesions of LPm itself left AChE staining nearly unchanged. Destruction of collicular neurons by excitotoxins dramatically reduced AChE staining in fibers of the brachium and superficial gray layer of the superior colliculus. The reduction was especially pronounced in the lower part of the superficial gray layer, in which LP-projecting collicular neurons are located. These results are consistent with the view that LP-projecting collicular neurons synthesize AChE and account for much of the histochemically detectable enzyme present both in the lower superficial gray layer and in LPm. In the colliculus, the excitotoxin lesions spared AChE staining in a thin sheet at the upper border of the superficial gray layer and in the enzyme-positive patches in the intermediate layers. This surviving tectal AChE thus is probably presynaptic and could be contained at least partly in cholinergic afferents from the parabigeminal nucleus and pontomesencephalic tegmentum. The collicular lesions had no obvious effect on AChE staining in the parabigeminal nucleus or in the C-laminae or ventral division of the lateral geniculate nucleus.
ESTHER : Berson_1991_Exp.Brain.Res_84_478
PubMedSearch : Berson_1991_Exp.Brain.Res_84_478
PubMedID: 1713853

Title : Intrastriatal grafts derived from fetal striatal primordia. III. Induction of modular patterns of fos-like immunoreactivity by cocaine - Liu_1991_Exp.Brain.Res_85_501
Author(s) : Liu FC , Dunnett SB , Robertson HA , Graybiel AM
Ref : Experimental Brain Research , 85 :501 , 1991
Abstract : Cocaine, a catecholamine agonist, has been shown to produce a transient induction of the immediate-early gene c-fos and its protein product Fos in the striatum of normal rats. In the present study we report that the expression of Fos can be induced by cocaine challenge in intrastriatal grafts derived from cell suspensions of embryonic striatal primordia. Fos-like immunoreactivity in the nuclei of grafted neurons was detected 2 hr after the injection of 50 mg/kg cocaine into the host rats. Neurons with Fos-immunoreactive nuclei tended to form clusters in the striatal grafts. The Fos-rich clusters were aligned with acetylcholinesterase (AChE)-rich and tyrosine hydroxylase (TH)-rich patches demonstrated in adjoining sections. Previous studies have shown that presynaptic and postsynaptic cellular markers of the dopaminergic system in the striatum, including immunostaining for TH and dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein (DARPP-32), and binding for high affinity dopamine uptake sites and for dopamine D1 and D2 receptor sites, are all concentrated in the AChE-rich patch regions (P regions) of such embryonic striatal grafts. The preferential expression of Fos in neurons of the P regions of the grafts thus implies that the induction of Fos was cell-type specific in being concentrated in the parts of the grafts that express striatal phenotype and that are innervated by catecholamine-containing fibers.(ABSTRACT TRUNCATED AT 250 WORDS)
ESTHER : Liu_1991_Exp.Brain.Res_85_501
PubMedSearch : Liu_1991_Exp.Brain.Res_85_501
PubMedID: 1680735

Title : Pharmacologically defined M1 and M2 muscarinic cholinergic binding sites in the cat's substantia nigra: development and maturity - Nastuk_1991_Brain.Res.Dev.Brain.Res_61_1
Author(s) : Nastuk MA , Graybiel AM
Ref : Brain Research Developmental Brain Research , 61 :1 , 1991
Abstract : Muscarinic cholinergic binding in the substantia nigra of the cat was documented during development and at maturity with autoradiographic methods by labeling the pharmacologically defined M1 and M2 subtypes of muscarinic binding sites. In cats from age embryonic day 40 to postnatal day 6 and at adulthood, M1 sites were labeled with [3H]pirenzepine and M2 sites were labeled with [3H]N-methylscopolamine in competition with pirenzepine. Comparisons were made among binding site distributions, acetylcholinesterase staining and tyrosine hydroxylase-like immunoreactivity in serial or neighboring nigral tissue sections. M1 and M2 binding sites were present in the substantia nigra at all ages studied. Qualitative comparisons showed that M1 binding delineated the substantia nigra more distinctly than did M2 binding. For M1 binding sites in particular, the embryonic pars reticulata of the substantia nigra was more prominently labeled than the pars compacta. At adulthood both nigral subdivisions clearly exhibited M1 and M2 binding, with the pars compacta demonstrating some internal heterogeneity of binding density. These findings provide further evidence that the substantia nigra is a site of cholinergic transmission and suggest that the functional balance between acetylcholine and dopamine in the basal ganglia acts here as well as in the striatum.
ESTHER : Nastuk_1991_Brain.Res.Dev.Brain.Res_61_1
PubMedSearch : Nastuk_1991_Brain.Res.Dev.Brain.Res_61_1
PubMedID: 1914150

Title : Location of saccade-related neurons in the macaque superior colliculus - Ma_1991_Exp.Brain.Res_85_21
Author(s) : Ma TP , Graybiel AM , Wurtz RH
Ref : Experimental Brain Research , 85 :21 , 1991
Abstract : The locations of saccade-related neurons were studied in the superior colliculi of two adult rhesus monkeys (Macaca mulatta) by placing marking lesions at the sites of physiologically characterized cells and comparing these histologically identified sites with the collicular laminae and acetylcholinesterase (AChE)-rich patches. Three major conclusions were drawn on the basis of 39 histologically identified sites at which saccade-related neurons were recorded. First, saccade-related neurons were distributed from the ventral half of the optic layer through the deep gray layer, and were most concentrated in the intermediate gray and white layers. Second, there was a clear relationship between the discharge characteristics of these saccade-related neurons and the depths at which they were found. Neurons having presaccadic bursts, defined as clipped and partially-clipped, tended to be encountered more dorsally, and neurons that did not have bursts (unclipped) were encountered more ventrally. Although cells having different discharge characteristics seemed to be organized along a dorsoventral axis, there was no compelling evidence that these properties were specified by their laminar locations. Third, there was no clear correlation between the locations of saccade-related neurons and the distribution of individual AChE-rich patches. Saccade-related cells were found both in the caudal superior colliculus where patches were located and in the rostral superior colliculus where patches were not found; both within and between the two tiers of AChE-rich patches in the caudal superior colliculus; and both within and between individual AChE-rich patches. However, the depth-level at which saccade-related neurons occurred generally matched the region bounded by the two tiers of AChE-rich patches in the intermediate and deep layers, and the dorsal and ventral extent of saccade-related neurons was the same as that of the AChE-rich patches.
ESTHER : Ma_1991_Exp.Brain.Res_85_21
PubMedSearch : Ma_1991_Exp.Brain.Res_85_21
PubMedID: 1715825

Title : Intrastriatal grafts derived from fetal striatal primordia: II. Reconstitution of cholinergic and dopaminergic systems - Liu_1990_J.Comp.Neurol_295_1
Author(s) : Liu FC , Graybiel AM , Dunnett SB , Baughman RW
Ref : Journal of Comparative Neurology , 295 :1 , 1990
Abstract : Reconstitution of striatal cholinergic and dopaminergic systems was studied in intrastriatal grafts derived from embryonic day 15 rat striatal primordia and implanted into adult host rats in which unilateral ibotenic acid lesions had previously been made in the striatum. Histochemical, immunohistochemical, and ligand binding autoradiographic techniques were applied to analyze different constituents of these two systems and to study their locations relative to each other in grafts allowed to grow for 9-17 months following transplantation. For the cholinergic system, a modular organization was found in the striatal grafts with stains for choline acetyltransferase and acetylcholinesterase, respectively the synthetic and degradative enzymes for cholinergic neurons; by autoradiographic [3H]hemicholinium binding, specific for high affinity choline uptake sites associated with cholinergic terminals; and by autoradiographic [3H]pirenzepine binding, selective for M1 receptors. For the dopaminergic system, a comparable modular organization was found in the grafts by immunostaining for tyrosine hydroxylase, the catecholamine synthetic enzyme; by autoradiographic [3H]mazindol binding for dopamine uptake sites; and by [3H]SCH23390 binding for dopamine D1 receptors and [3H]sulpiride binding for dopamine D2 receptors. The results indicate that the distributions of the cholinergic and dopaminergic markers in striatal grafts are in close anatomical register. These markers for intracellular and membrane-associated components of the cholinergic and dopaminergic systems were preferentially localized in the acetylcholesterase-rich patches of the grafts in which cortical and thalamic fibers have also been found in striatal grafts, and in which output neurons projecting to the pallidum are located. This anatomical correlation suggests that the substrates for cholinergic-dopaminergic interactions typical of the normal striatum may be reinstated in the grafts both in relation to efferent neurons establishing connections with the host brain that are typical of normal striatofugal connections, and in relation to major afferent fiber systems from the host brain originating in regions known to project densely to the normal striatum. Accordingly, the cholinergic and dopaminergic systems in such grafts may regulate the functional influence of the grafts on the behavior of host animals.
ESTHER : Liu_1990_J.Comp.Neurol_295_1
PubMedSearch : Liu_1990_J.Comp.Neurol_295_1
PubMedID: 1971286

Title : Ontogeny of M1 and M2 muscarinic binding sites in the striatum of the cat: relationships to one another and to striatal compartmentalization - Nastuk_1989_Neurosci_33_125
Author(s) : Nastuk MA , Graybiel AM
Ref : Neuroscience , 33 :125 , 1989
Abstract : The ontogeny of striatal M1 and M2 muscarinic cholinergic binding sites was studied autoradiographically in cats ranging in age from embryonic day 40 to postnatal day six. Direct labeling with [3H]pirenzepine revealed M1 sites, and M2 sites were labeled with [3H]N-methylscopolamine in the presence of pirenzepine. In serial tissue sections, distributions of striatal M1 and M2 sites were compared to one another and to patterns of acetylcholinesterase staining and tyrosine hydroxylase-like immunoreactivity. The younger fetal material demonstrated heterogeneous distributions for both subtypes of muscarinic binding sites, with patches of dense binding corresponding to islands of dopaminergic nigrostriatal innervation. For both M1 and M2 binding, lateral to medial and caudal to rostral density gradients were present in the patches and in the surrounding matrix. During fetal development and into the perinatal period, overall muscarinic binding increased, but more so in the matrix than in the patches. By postnatal day six striatal M2 binding appeared nearly homogeneous. M1 binding, however, was slightly more concentrated in patches than in matrix. The patches of elevated M1 binding were still present at maturity, and corresponded to striosomes. These findings suggest that the ontogenetic regulation of muscarinic binding sites is influenced by location relative to striatal compartments, and that expression of M1 and M2 binding site subtypes is differentially regulated.
ESTHER : Nastuk_1989_Neurosci_33_125
PubMedSearch : Nastuk_1989_Neurosci_33_125
PubMedID: 2601852

Title : Intrastriatal grafts derived from fetal striatal primordia. I. Phenotypy and modular organization - Graybiel_1989_J.Neurosci_9_3250
Author(s) : Graybiel AM , Liu FC , Dunnett SB
Ref : Journal of Neuroscience , 9 :3250 , 1989
Abstract : Fetal striatal grafts display a striking modularity of composition. With acetylcholinesterase (AChE) histochemistry, the tissue of such grafts can be divided into regions with strong AChE staining of the neuropil and regions in which AChE staining of the neuropil is weak. In the experiments reported here, we reexamined the nature of this modularity. Striatal grafts were made by injecting dissociated cells of E15 ganglionic eminence into the striatum of adult rats, which 7 days before had recived intrastriatal deposits of ibotenic acid. Some donors had been exposed to 3H-thymidine at E11-E15. After 9-17 month survivals, the anatomical organization of the grafts was studied by histochemistry, immunohistochemistry, and autoradiography. In every graft, the AChE-rich regions formed patches (P regions) in a larger AChE-poor surround (NP regions). Neurons labeled with 3H-thymidine appeared in both P and NP regions, suggesting that donor cells were distributed in each type of region and that neither type of tissue, P or NP, was composed exclusively of host tissue. In the AChE-rich P regions, markers characteristic of normal perinatal and mature rat striatum were expressed by medium-sized cells: calcium-binding protein (calbindin D28k) immunostaining, metenkephalin (mENK) immunostaining, and, more rarely, somatostatin (SOM) immunostaining. In the NP regions, however, medium-sized cells expressing calbindin and mENK immunostaining were very rare, and there was an abundance of neuronal types not found in normal mature striatal tissue. These included (1) large, multipolar, calbindin-positive neurons with well-ramified, densely stained dendrites, (2) large, SOM-positive neurons with prominent dendritic trees, and (3) mENK-positive cells smaller than typical striatal, medium-sized, mENK-immunoreactive neurons. In Nissl stains, the AChE-rich P regions resembled the normal striatum of mature animals, whereas the AChE-poor NP regions did not. These findings suggest that the P regions of fetal striatal grafts achieve a phenotypy similar to that of normal striatum at maturity and during much of postnatal development. The dominant expression of perikaryal calbindin-like immunoreactivity in the P regions further suggests that these zones have a high proportion of tissue resembling striatal matrix. By contrast, expression of marker antigens in the NP zones of the grafts suggests that these zones are predominantly composed of nonstriatal tissue or that they have the phenotypy of immature striatum intermixed with some nonstriatal cells.(ABSTRACT TRUNCATED AT 400 WORDS)
ESTHER : Graybiel_1989_J.Neurosci_9_3250
PubMedSearch : Graybiel_1989_J.Neurosci_9_3250
PubMedID: 2477513

Title : Dopamine uptake sites in the striatum are distributed differentially in striosome and matrix compartments - Graybiel_1989_Proc.Natl.Acad.Sci.U.S.A_86_9020
Author(s) : Graybiel AM , Moratalla R
Ref : Proc Natl Acad Sci U S A , 86 :9020 , 1989
Abstract : A major mechanism of neurotransmitter inactivation at catecholaminergic synapses is reuptake of released transmitter at high-affinity uptake sites on presynaptic terminals. We have analyzed the anatomical distribution of site-selective ligand binding for dopamine uptake sites in the striatum of rat, cat, and monkey. We report here that desipramine-sensitive [3H]mazindol binding sites have highly heterogeneous distributions in the dorsal and the ventral striatum. In the caudate nucleus of cat and monkey, [3H]mazindol binding observes striosomal ordering, being reduced in striosomes and heightened in the extrastriosomal matrix. Some local heterogeneity appears in the ventral caudoputamen of the rat. Different subdivisions of the nucleus accumbens also have different binding levels. These findings suggest that some functional effects of psychoactive drugs, such as cocaine, that bind to the dopamine-uptake complex could be related to the distribution of these specific uptake sites. The findings also raise the possibility that these distributions could result in selective neuronal vulnerability to neurotoxins, such as 1-methyl-4-phenylpyridine (MPP+), that depend on the dopamine-uptake complex for entry into neurons.
ESTHER : Graybiel_1989_Proc.Natl.Acad.Sci.U.S.A_86_9020
PubMedSearch : Graybiel_1989_Proc.Natl.Acad.Sci.U.S.A_86_9020
PubMedID: 2813436

Title : Compartmental origins of striatal efferent projections in the cat - Jimenez-Castellanos_1989_Neurosci_32_297
Author(s) : Jimenez-Castellanos J , Graybiel AM
Ref : Neuroscience , 32 :297 , 1989
Abstract : Injections of the retrograde tracer, wheat germ agglutinated-horseradish peroxidase were placed in the substantia nigra, in adjoining dopamine-containing cell groups A8 and A10, and in the internal and external parts of the pallidal complex of 20 cats in order to identify the compartmental origins of striatal efferent projections to the pallidum and midbrain. Patterns of retrograde cell-labeling in the caudate nucleus were analysed with respect to its striosomal architecture as detected in sections stained for acetylcholinesterase. Where possible, a similar compartmental analysis of cell-labeling in the putamen was also carried out. In 15 cats anterograde labeling in the striatum was studied in the sections stained with wheat germ agglutinated-horseradish peroxidase or in autoradiographically treated sections from cases in which [35S]methionine was mixed with the wheat germ agglutinated-horseradish peroxidase in the injection solution. Predominant labeling of projection neurons lying in striosomes (usually with some labeling of dorsomedial matrix neurons) occurred in a subset of the cases of nigral injection, including all cases (n = 9) in which the injection sites were centered in the densocellular zone of the substantia nigra pars compacta [Jimenez-Castellanos J. and Graybiel A. M. (1987) Neuroscience 23, 223-242.] Dense labeling of neurons in the extrastriosomal matrix, with at most sparse labeling of striosomal neurons, occurred in all cases of pallidal injection (n = 8) and in two cases of nigral injection in which the injection sites were lateral and anterior to the densocellular zone. Mixed labeling of striosomal and matrical neurons occurred in a third group of cases in which the injection sites were lateral to the densocellular zone but close to it. In a single case with an injection site situated in the pars lateralis of the substantia nigra, there was preferential labeling of striosomal neurons in the caudal caudate nucleus but widespread labeling of neurons in both striosomes and matrix in the putamen. A second type of compartmental ordering of projection neurons was found in the extrastriosomal matrix of the striatum. In cases of pallidal and nigral injection, there were gaps in cell labeling that did not match striosomes precisely, and often clusters of labeled cells appeared that did not correspond to acetylcholinesterase-poor striosomes but, instead, to patches of matrix. Especially prominent were clusters beside striosomes. There was a topographic ordering of striatal projection neurons both in the striosomes and in the extrastriosomal matrix according to their dorsoventral and latitudinal positions.(ABSTRACT TRUNCATED AT 400 WORDS)
ESTHER : Jimenez-Castellanos_1989_Neurosci_32_297
PubMedSearch : Jimenez-Castellanos_1989_Neurosci_32_297
PubMedID: 2479881

Title : Evidence that histochemically distinct zones of the primate substantia nigra pars compacta are related to patterned distributions of nigrostriatal projection neurons and striatonigral fibers - Jimenez-Castellanos_1989_Exp.Brain.Res_74_227
Author(s) : Jimenez-Castellanos J , Graybiel AM
Ref : Experimental Brain Research , 74 :227 , 1989
Abstract : A marked histochemical compartmentalization is visible in the substantia nigra of the squirrel monkey in sections stained for acetylcholinesterase (AChE). In nigral regions containing tyrosine hydroxylase-positive neurons, there are AChE-poor and AChE-rich zones, and many of the AChE-poor zones have the form of narrow fingers extending ventrally into an AChE-rich matrix (Jimenez-Castellanos and Graybiel 1987b). The study reported here was carried out to determine whether this histochemical heterogeneity of the primate's substantia nigra is related to the known differentiation within its pars compacta of subdivisions projecting respectively to the caudate nucleus and to the putamen. Retrograde and anterograde labeling in the substantia nigra was elicited by tracer injections placed in the caudate nucleus or putamen and was plotted in relation to patterns of AChE staining and tyrosine hydroxylase immunostaining. Much of the labeling observed was organized according to borders visible with AChE histochemistry: labeled nigral neurons (and afferent fibers) tended to be clustered precisely within the AChE-poor ventrally-extending fingers or to be situated outside these zones. However, projection neurons in these ventrally-extending fingers were not exclusively related either to the caudate nucleus or to the putamen. After injections in the caudate nucleus, labeled neurons were predominantly in the AChE-poor fingers in some cases, but predominantly in AChE-rich nigral zones outside them in other cases. Labeling in and out of the ventrally-extending fingers, and along the edges of the fingers, also occurred following different tracer injections in the putamen. These findings confirm the independent clustering of nigrostriatal neurons projecting respectively to the caudate nucleus and to the putamen. The plan of nigrostriatal connections additionally appears concordant with the histochemical compartmentalization of the substantia nigra that can be detected with acetylthiocholinesterase histochemistry.
ESTHER : Jimenez-Castellanos_1989_Exp.Brain.Res_74_227
PubMedSearch : Jimenez-Castellanos_1989_Exp.Brain.Res_74_227
PubMedID: 2466685

Title : Striosomes and extrastriosomal matrix contain different amounts of immunoreactive choline acetyltransferase in the human striatum - Hirsch_1989_Neurosci.Lett_96_145
Author(s) : Hirsch EC , Graybiel AM , Hersh LB , Duyckaerts C , Agid Y
Ref : Neuroscience Letters , 96 :145 , 1989
Abstract : Cholinergic neuropil and cell bodies were identified in the human striatum by immunohistochemistry carried out with a polyclonal antibody raised against choline acetyltransferase (ChAT). The cholinergic neuropil was not uniformly distributed in the striatum, and especially in the caudate nucleus ChAT-poor zones corresponding to acetylcholinesterase (AChE)-poor striosomes were identified. Striosomal organization of ChAT-positive neuropil was also detected in striatal tissue from patients who had suffered parkinsonian and choreic disorders.
ESTHER : Hirsch_1989_Neurosci.Lett_96_145
PubMedSearch : Hirsch_1989_Neurosci.Lett_96_145
PubMedID: 2522606

Title : [3H]SCH 23390 binding to D1 dopamine receptors in the basal ganglia of the cat and primate: delineation of striosomal compartments and pallidal and nigral subdivisions - Besson_1988_Neurosci_26_101
Author(s) : Besson MJ , Graybiel AM , Nastuk MA
Ref : Neuroscience , 26 :101 , 1988
Abstract : The distribution of D1 dopamine receptors was studied autoradiographically in the basal ganglia of the cat, monkey and human. These receptor binding sites were labeled directly with the D1-selective antagonist [3H]SCH 23390, and ligand-binding assays were performed concurrently. Serial- or same-action analysis permitted comparisons among D1 binding distributions, acetylcholinesterase staining and tyrosine hydroxylase immunoreactivity. In all species studied, the dorsal striatum exhibited patches of particularly dense D1 binding in correspondence with acetylcholinesterase-poor striosomes. Highly patterned binding was present in the ventral striatum. Distinctions in binding density were observed among the subdivisions of the globus pallidus and of the substantia nigra. The external segment of the pallidum was extremely sparse in D1 binding, whereas the internal segment (or entopeduncular nucleus in the cat) was a site of high D1 binding density. The binding density was greatest in the core of the internal segment, and tyrosine hydroxylase-positive fibers surrounded and weakly dispersed themselves through this core. Weak binding was present in the ventral pallidum. In the substantia nigra, the pars reticulata demonstrated the densest binding, particularly medially. The pars compacta showed much sparser binding, though some of its tyrosine hydroxylase-positive neurons had dendrites extending ventrally into the zone of dense D1 binding in the pars reticulata. We conclude that [3H]SCH 23390-defined D1 binding is compartmentalized in the dorsal striatum and that, particularly in relation to the reported distributions of striatal D2 dopamine receptors, this is likely to be of functional significance in the dopaminergic modulation of intrastriatal neurotransmission as well as of afferent and efferent neurotransmission. The segregated localizations of D1 receptors in the substantia nigra suggest predominant activation of the pars reticulata, including ventral and medial regions adjacent to the densocellular zone. Specific pathways from compartments in the striatum to subdivisions of the pallidum may also be differentially modulated by dopamine acting via distinct receptor subtypes. At the level of the pallidum, such D1 modulation appears to be restricted to the internal segment, which projects to the thalamus, rather than to the external pallidum, which projects to the subthalamic nucleus.
ESTHER : Besson_1988_Neurosci_26_101
PubMedSearch : Besson_1988_Neurosci_26_101
PubMedID: 2901690

Title : Autoradiographic localization and biochemical characteristics of M1 and M2 muscarinic binding sites in the striatum of the cat, monkey, and human - Nastuk_1988_J.Neurosci_8_1052
Author(s) : Nastuk MA , Graybiel AM
Ref : Journal of Neuroscience , 8 :1052 , 1988
Abstract : The autoradiographic distribution of M1 and M2 muscarinic cholinergic binding sites was studied in the striatum of the cat, monkey, and human, and concurrent binding assays were carried out on striatal tissue sections from the cat. M1 sites were directly labeled with 3H-pirenzepine; M2 sites were labeled as a consequence of binding competition between pirenzepine and 3H-N-methylscopolamine. Serial section analysis with autoradiograms and stained tissue sections allowed for comparisons among M1 and M2 binding distributions and AChE staining patterns. The 2 subtypes of binding sites demonstrated distinct striatal distributions. M2 sites were virtually homogeneous except in the ventral striatum, where zones of sparse and especially dense binding were observed. Striatal M1 sites were generally more abundant than M2 sites and showed similar heterogeneity in the ventral striatum. Dorsally, however, patches of dense M1 binding were found, and proved to correspond with AChE-poor striosomes, hallmarks of striatal compartmentalization. The finding of differing distributions for the 2 subtypes of muscarinic cholinergic binding sites suggests a mechanism for the intrinsic spatial segregation of striatal cholinergic function. Further, the striosomal patterning of M1 binding indicates that certain aspects of cholinergic function in the striatum may be constrained and thus regulated by the compartmental ordering characteristic of this region of the basal ganglia.
ESTHER : Nastuk_1988_J.Neurosci_8_1052
PubMedSearch : Nastuk_1988_J.Neurosci_8_1052
PubMedID: 3346715

Title : Cellular substrate of the histochemically defined striosome\/matrix system of the caudate nucleus: a combined Golgi and immunocytochemical study in cat and ferret - Bolam_1988_Neurosci_24_853
Author(s) : Bolam JP , Izzo PN , Graybiel AM
Ref : Neuroscience , 24 :853 , 1988
Abstract : In order to learn what morphological substrate might underly the histochemical compartments of the neostriatum, sections of the caudate nucleus and the putamen of cats and ferrets were stained immunocytochemically with antisera directed against several neuropeptides and transmitter-related enzymes and were then Golgi-impregnated. Adjacent sections were stained to reveal acetylcholinesterase activity to identify the acetylcholinesterase-poor striosomes. The immunostaining produced by several of the antibody preparations was in register with the acetylcholinesterase-poor striosomes but the most prominent staining of these zones occurred with the antibodies directed against substance P. The striosomes were delineated by intense substance P-immunostaining of neuronal perikarya and dendrites, and in the rostral and dorsal caudate nucleus the boundary between substance P-immunostained and extrastriosomal matrix was abrupt. For these reasons we analysed Golgi-impregnated neurons in sections immunostained for substance P in order to assess the influence of the chemically defined striosomal architecture on the position and dendritic arborization of neurons located both within the striosomes and within the extrastriosomal matrix. The most commonly impregnated neurons were of the medium-size densely spiny class. Those that were present within the striosomes and lay within one dendritic radius of the boundary were divided into two types: (1) neurons whose dendritic arborization was apparently not influenced by the boundary and (2) neurons whose dendritic arborization was markedly influenced by the boundary. For neurons of the latter type, dendrites either emerged from the parts of the perikaryon away from the boundary, so avoiding crossing it, or they exhibited abrupt changes in their course, apparently to avoid crossing the boundary. Spiny neurons located in the extrastriosomal matrix but close to the striosomal boundary had dendrites that were either influenced by, or not influenced by the compartmental boundary. We conclude that there is a specific cytoarchitecture underlying the histochemical compartments of the neostriatum and that different sub-populations of medium-size spiny neurons underly (1) the segregation of information flow in striosomes and the extrastriosomal matrix and (2) communication between striosomes and the extrastriosomal matrix.
ESTHER : Bolam_1988_Neurosci_24_853
PubMedSearch : Bolam_1988_Neurosci_24_853
PubMedID: 2454418

Title : Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease - Hirsch_1988_Nature_334_345
Author(s) : Hirsch E , Graybiel AM , Agid YA
Ref : Nature , 334 :345 , 1988
Abstract : In idiopathic Parkinson's disease massive cell death occurs in the dopamine-containing substantia nigra. A link between the vulnerability of nigral neurons and the prominent pigmentation of the substantia nigra, though long suspected, has not been proved. This possibility is supported by evidence that N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its metabolite MPP+, the latter of which causes destruction of nigral neurons, bind to neuromelanin. We have directly tested this hypothesis by a quantitative analysis of neuromelanin-pigmented neurons in control and parkinsonian midbrains. The findings demonstrate first that the dopamine-containing cell groups of the normal human midbrain differ markedly from each other in the percentage of neuromelanin-pigmented neurons they contain. Second, the estimated cell loss in these cell groups in Parkinson's disease is directly correlated (r = 0.97, P = 0.0057) with the percentage of neuromelanin-pigmented neurons normally present in them. Third, within each cell group in the Parkinson's brains, there is greater relative sparing of non-pigmented than of neuromelanin-pigmented neurons. This evidence suggests a selective vulnerability of the neuromelanin-pigmented subpopulation of dopamine-containing mesencephalic neurons in Parkinson's disease.
ESTHER : Hirsch_1988_Nature_334_345
PubMedSearch : Hirsch_1988_Nature_334_345
PubMedID: 2899295

Title : Fibers from the basolateral nucleus of the amygdala selectively innervate striosomes in the caudate nucleus of the cat - Ragsdale_1988_J.Comp.Neurol_269_506
Author(s) : Ragsdale CW, Jr. , Graybiel AM
Ref : Journal of Comparative Neurology , 269 :506 , 1988
Abstract : The compartmental organization of the amygdalostriatal projection was studied in the cat by comparing staining patterns seen by cholinesterase enzyme histochemistry with the distribution of fibers labelled with a horseradish peroxidase-wheat germ agglutinin conjugate or by incorporation of 35S-methionine or 3H-leucine. Fibers from the basolateral nucleus of the amygdala were found to innervate selectively acetylcholinesterase-poor striosomes demonstrated in the caudate nucleus and butyrylcholinesterase-rich zones observed in the anterodorsal nucleus accumbens. In no case were the amygdalar fibers fully restricted to striosomes, but the nature and degree of labelling of the striatal matrix, as well as the range of the labelled fibers in dorsal striatum, varied with the positions of the injection sites.
ESTHER : Ragsdale_1988_J.Comp.Neurol_269_506
PubMedSearch : Ragsdale_1988_J.Comp.Neurol_269_506
PubMedID: 2453535

Title : Subdivisions of the dopamine-containing A8-A9-A10 complex identified by their differential mesostriatal innervation of striosomes and extrastriosomal matrix - Jimenez-Castellanos_1987_Neurosci_23_223
Author(s) : Jimenez-Castellanos J , Graybiel AM
Ref : Neuroscience , 23 :223 , 1987
Abstract : The mesostriatal projections from the dopamine-containing cells groups A8, A9 and A10 have been studied in the cat in relation to the histochemical compartments known to exist in the striatum. In order to do this, we made stereotaxic injections in the substantia nigra of either [3H]proline-[3H]leucine, [35S]methionine, wheat germ agglutinin-horseradish peroxidase, or the two last tracers combined, and compared the location of anterograde labeling in the striatum to the locations of striosomes and extrastriosomal matrix identified by their low or high content, respectively, of the enzyme acetylcholinesterase. A discrete innervation of dorsolateral striosomes by a caudal densocellular subdivision of the substantia nigra pars compacta was found. This densocellular zone of the pars compacta was readily identifiable in sections stained for tyrosine hydroxylase-like immunoreactivity and corresponded to the uniquely acetylcholinesterase-poor zone detected in the substantia nigra pars compacta in serially adjacent sections stained for this enzyme. Selective anterograde labeling of the extrastriosomal matrix occurred in cases with injection sites centered in cell group A8. Tracer deposits in cell group A10 also elicited a preferential labeling of the extrastriosomal matrix, but this innervation was sparse compared to the prominent labeling of fibers in the ventral striatum. An almost exclusive innervation of caudal and ventral striosomes of the head of the caudate nucleus occurred after a deposit of tracer in the pars lateralis of the substantia nigra. Mixed labeling of striosomes and matrix occurred with injection sites centered in the rostral, cell-sparse part of the pars compacta of the substantia nigra. Clusters of tyrosine hydroxylase-immunoreactive neurons within this zone, most likely representing finger-like extensions of the caudal densocellular zone of the pars compacta, might have accounted for part of the striosomal labeling in these cases. We conclude that different subdivisions of the A8-A9-A10 dopamine-containing cell complex of the cat's mesencephalon project preferentially to striosomes or to extrastriosomal matrix. On this basis we suggest that there may be different functional channels in the mesostriatal projection, including, from cell group A8, a channel providing dopaminergic modulation of sensorimotor processing in the striatal matrix, and, from the densocellular zone of the substantia nigra pars compacta, a channel leading to limbic-related mechanisms represented in the striosomal system.
ESTHER : Jimenez-Castellanos_1987_Neurosci_23_223
PubMedSearch : Jimenez-Castellanos_1987_Neurosci_23_223
PubMedID: 3683862

Title : Subdivisions of the primate substantia nigra pars compacta detected by acetylcholinesterase histochemisty - Jimenez-Castellanos_1987_Brain.Res_437_349
Author(s) : Jimenez-Castellanos J , Graybiel AM
Ref : Brain Research , 437 :349 , 1987
Abstract : Acetylcholinesterase-poor and acetylcholinesterase-rich compartments have been identified histochemically in the substantia nigra pars compacta of the squirrel monkey. Some of these compartments have clear correspondents in sections immunostained for tyrosine hydroxylase and in sections stained for Nissl substance. Clustering patterns of neurons retrogradely labeled after tracer injections either in the caudate nucleus or in the putamen were found to be related to these histochemical and cytoarchitectonic specializations of the substantia nigra pars compacta.
ESTHER : Jimenez-Castellanos_1987_Brain.Res_437_349
PubMedSearch : Jimenez-Castellanos_1987_Brain.Res_437_349
PubMedID: 2449266

Title : A new enzyme marker for striatal compartmentalization: NADPH diaphorase activity in the caudate nucleus and putamen of the cat - Sandell_1986_J.Comp.Neurol_243_326
Author(s) : Sandell JH , Graybiel AM , Chesselet MF
Ref : Journal of Comparative Neurology , 243 :326 , 1986
Abstract : The distribution of dihydronicotinamide adenine dinucleotide phosphate diaphorase (NADPH diaphorase) was studied by enzyme histochemistry in the striatum of the adult cat. Neurons and neuropil expressing NADPH diaphorase activity were found throughout the striatum. The diaphorase-positive neurons formed a sparse population of medium-sized cells. In the caudate nucleus they were recognized by antisera against somatostatin 14, somatostatin 28(1-12), neuropeptide Y and avian pancreatic polypeptide. The diaphorase activity of the striatal neuropil was characterized by a modular organization that was particularly distinct in the caudate nucleus. This organization was analyzed by comparing the patterns of diaphorase staining with the distribution of acetylcholinesterase activity in adjacent sections. The NADPH diaphorase activity was found to be dense in the acetylcholinesterase-rich matrix of the caudate nucleus, but weak in the acetylcholinesterase-poor compartments known as striosomes. Because of the colocalization of perikaryal NADPH diaphorase activity and somatostatinlike immunoreactivity, a comparison was also made between the distribution of diaphorase staining and immunostaining for somatostatinlike peptide in the striatal neuropil. Both observed striosomal ordering, so that the acetylcholinesterase-poor zones detected in adjoining sections corresponded to regions of low somatostatinlike immunoreactivity as well as low NADPH diaphorase staining. In some regions striosomes were more clearly delineated in the stains for diaphorase and somatostatinlike suggest that NADPH diaphorase may be a sensitive marker for the somatostatinergic neuropil as well as the somatostatinergic perikarya of the striatum, and that this enzyme could prove valuable in attempts to differentiate the processes of intrinsic somatostatin-containing fibers from any extrinsic somatostatin afferents that may exist.
ESTHER : Sandell_1986_J.Comp.Neurol_243_326
PubMedSearch : Sandell_1986_J.Comp.Neurol_243_326
PubMedID: 2419368

Title : Complementary and non-matching afferent compartments in the cat's superior colliculus: innervation of the acetylcholinesterase-poor domain of the intermediate gray layer - Illing_1986_Neurosci_18_373
Author(s) : Illing RB , Graybiel AM
Ref : Neuroscience , 18 :373 , 1986
Abstract : Three tectal afferent-fiber systems were experimentally labeled in the cat to learn how their distributions within the superior colliculus were related to the prominent compartments of high acetylcholinesterase activity found in the intermediate gray layer. Presumptive somatic sensory afferents were labeled by injections of horseradish peroxidase-wheatgerm agglutinin conjugate placed at the bulbospinal junction and in the ventral anterior ectosylvian cortex corresponding to somatic sensory area SIV. Vision-related afferents were labeled by injections of the same tracer substance into the lateral suprasylvian visual area. In each animal, a single type of injection was made and a detailed study was carried out to compare the patterns of anterograde labeling and acetylcholinesterase staining in serially adjoining sections through the superior colliculus. Fibers labeled by the three types of injection were distributed in clusters that resembled the acetylcholinesterase-positive patches in the intermediate gray layer. In no case, however, were the afferent-fiber clusters in register with the histochemically defined patches. Instead, the innervations derived from the bulbospinal junction, anterior estosylvian sulcus and lateral suprasylvian visual area all formed patchworks within the acetylcholinesterase-poor domain of the intermediate gray layer. In some instances, the afferent-fiber clusters and enzyme-positive patches appeared to have complementary distributions. In other instances, the afferent-fiber clusters seemed to be arranged in the acetylcholinesterase-poor parts of the intermediate layer in a fashion independent of, but not significantly overlapping, the acetylcholinesterase-positive patches. Not all of the space between the acetylcholinesterase-positive patches was taken up by any one of the afferent-fiber systems labeled. The complementary and non-matching distribution of these afferent systems in relation to the acetylcholinesterase-rich patches of the intermediate gray layer stands in contrast to the spatial registration of two other tectal afferent systems with the zones of high acetylcholinesterase activity. Both nigrotectal and frontotectal afferents converge on the acetylcholinesterase-positive patches. We conclude that afferent systems projecting to the intermediate gray layer can be divided into at least two groups: those innervating the acetylcholinesterase-rich compartments and those avoiding them.(ABSTRACT TRUNCATED AT 400 WORDS)
ESTHER : Illing_1986_Neurosci_18_373
PubMedSearch : Illing_1986_Neurosci_18_373
PubMedID: 3736863

Title : Neuropeptides in the basal ganglia -
Author(s) : Graybiel AM
Ref : Res Publ Assoc Res Nerv Ment Dis , 64 :135 , 1986
PubMedID: 2425403

Title : Cholinergic neuropil of the striatum observes striosomal boundaries - Graybiel_1986_Nature_323_625
Author(s) : Graybiel AM , Baughman RW , Eckenstein F
Ref : Nature , 323 :625 , 1986
Abstract : Acetylcholine and dopamine are key neurotransmitters in the extrapyramidal motor system, where they are thought to lie in a 'functional balance' brought about by interactions between the terminals of the dopamine-containing nigrostriatal tract and the cholinergic interneurones of the striatum. The precise nature of these interactions is not understood, however, nor is it clear how they influence the functioning of striatal systems containing other neurotransmitters. A new clue to understanding such interplay among transmitter-coded systems in the striatum has come from the finding that many of them, including nigrostriatal afferents, follow a macroscopic ordering in which neural elements are concentrated either in or out of the striatal tissue compartments called striosomes. We here report that the cholinergic neuropil of the striatum is also compartmentalized: fibres expressing immunoreactivity to antibodies raised against choline acetyltransferase (ChAT) are sparse in striosomes and are dense in the extrastriosomal matrix. These findings suggest that the interactions between acetylcholine and other neurotransmitters in the striatum are spatially constrained, that cholinergic modulation of striatal function predomintes in the extrastriosomal matrix, and that extrapyramidal pathways originating in the matrix, including transthalamic pathways to the frontal lobes, may in particular reflect this cholinergic influence. Such a differential organization of striatal cholinergic circuitry could help to account for the selective therapeutic efficacy of anticholinergic drugs in the treatment of extrapyramidal disorders.
ESTHER : Graybiel_1986_Nature_323_625
PubMedSearch : Graybiel_1986_Nature_323_625
PubMedID: 3773990

Title : Poster: Autoradiography of M, and M2 muscarinic binding in the striatum -
Author(s) : Nastuk MA , Graybiel AM
Ref : Trends in Pharmacological Sciences , Suppl :92 , 1986

Title : Striatal neurons expressing somatostatin-like immunoreactivity: evidence for a peptidergic interneuronal system in the cat - Chesselet_1986_Neurosci_17_547
Author(s) : Chesselet MF , Graybiel AM
Ref : Neuroscience , 17 :547 , 1986
Abstract : Neurons expressing immunoreactivity to antisera against somatostatin 14 and other somatostatin-related peptides were identified in the striatum of cats and nonhuman primates. In each species, immunoreactive neurons were distributed singly and in small groups in the caudate nucleus, putamen and ventral striatum. A detailed study was made of somatostatin-positive neurons and neuropil in the caudate nucleus of the cat. First, the mean diameters and surface areas of neurons expressing immunoreactivity to somatostatin 14 were made from peroxidase-antiperoxidase stained material. Second, fluorescence immunohistochemistry was combined with retrograde labeling of striatal neurons to determine whether such somatostatin 14-positive neurons emit axons projecting out of the striatum. Third, the distributions of neurons and neuropil expressing immunoreactivity to somatostatin 14 or somatostatin 28 (1-12) were plotted in relation to the locations of acetylcholinesterase-poor zones ("striosomes") visible in adjoining sections. The morphometric analysis suggested that somatostatin 14-positive neurons in the caudate nucleus form a single population of medium to medium-large neurons having mean diameters of 20 micron and mean surface areas of 154 micron2. The retrograde tracer study suggested that these somatostatin 14-positive neurons are interneurons. Injections of fast blue into all of the known targets of striatofugal fiber projections failed to label somatostatin 14-positive neurons save in a few instances (less than 0.3% of more than 4000 neurons) in each of which labeling was equivocal. Analysis of the distribution of somatostatin-positive neurons and neuropil in the striatum demonstrated that both observe striosomal ordering. Somatostatin immunoreactive neuropil was dense outside and weak inside identified striosomes, and most immunoreactive neurons lay outside. Often somatostatin-positive neurons lay beside, and sometimes striosomes partly rimmed them. The processes of such neurons tended to run along the borders of the striosomes without crossing them, but occasionally single processes and rarely entire dendritic trees crossed from one compartment to the other. These results suggest that, in the striatum of the cat, somatostatin is present: (1) in fibers organized according to the compartmental distribution already recognized for other neurochemical compounds in the striatum as well as for its afferent and efferent systems, and (2) in interneurons, mostly present in the extrastriosomal matrix, but also located near striosomes, where they could serve as interfaces between the striosomes and extrastriosomal matrix.
ESTHER : Chesselet_1986_Neurosci_17_547
PubMedSearch : Chesselet_1986_Neurosci_17_547
PubMedID: 2422590

Title : Convergence of afferents from frontal cortex and substantia nigra onto acetylcholinesterase-rich patches of the cat's superior colliculus - Illing_1985_Neurosci_14_455
Author(s) : Illing RB , Graybiel AM
Ref : Neuroscience , 14 :455 , 1985
Abstract : The patterns of distribution of frontotectal and nigrotectal fibers were studied with the anterograde horseradish peroxidase method in the cat. Direct serial-section comparisons were made between the afferent-fiber patterns and the compartmentalized arrangements of acetylcholinesterase staining within the intermediate and deep collicular layers. Many of the patches of high acetylcholinesterase activity in the intermediate gray layer proved to be zones in which labeled frontotectal and nigrotectal fibers converged. These acetylcholinesterase-rich patches may thus represent sites at which functional influences from the basal ganglia and frontal cortex are coordinated. In the deeper tiers of the intermediate gray layer and layers ventral to it, there were also zones of heightened and diminished acetylcholinesterase staining. Much of this histochemical patterning was reflected in the arrangement of fibers labeled by large rostromedial frontal injections, but these deeper tiers were not strongly labeled after more lateral frontal injections or after injections placed in the substantia nigra. The deeper parts of the acetylcholinesterase-positive gridwork in the superior colliculus are thus distinct from its upper tier of acetylcholinesterase-positive patches. We conclude that the compartmentalized patterning of dense acetylcholinesterase staining in the intermediate and deep collicular layers represents a mosaic architecture to which collicular afferent circuitry is tightly related. This gridwork may serve to set up functional domains within which different aspects of collicular processing are accommodated.
ESTHER : Illing_1985_Neurosci_14_455
PubMedSearch : Illing_1985_Neurosci_14_455
PubMedID: 3990954

Title : Patterns of muscarinic cholinergic binding in the striatum and their relation to dopamine islands and striosomes - Nastuk_1985_J.Comp.Neurol_237_176
Author(s) : Nastuk MA , Graybiel AM
Ref : Journal of Comparative Neurology , 237 :176 , 1985
Abstract : The distribution of muscarinic cholinergic binding sites in the striatum was studied in relation to the locations of other neurochemical markers in the developing rat, cat, ferret, and human. In addition, patterns of striatal muscarinic binding were studied in the adult cat. Receptor binding autoradiography was carried out with tritiated propylbenzilylcholine mustard [( 3H]-PrBCM), an irreversible muscarinic antagonist, and subsequent serial section analyses involved comparisons among patterns of muscarinic binding, catecholamine histofluorescence, acetylcholinesterase (AChE) staining, Nissl staining, and cell labeling with [3H]-thymidine. Muscarinic binding in the immature striatum was characterized by local patchiness as well as regional density gradients in all species, with the most complex patterns appearing in the human. Patches of dense muscarinic binding were shown to lie in register with fluorescent dopamine islands (rat, cat, ferret), with AChE-positive patches (all species), and with clusters of neurons pulse-labeled by exposure to [3H]-thymidine on embryonic day 27 (ferret). At the developmental stages examined, the [3H]-PrBCM-positive patches were roughly aligned with regions of weak Nissl staining (cat, human). Striatal [3H]-PrBCM binding in the adult cat was dense, and though it usually appeared nearly homogeneous, in some sections patches of elevated binding were present. These had as counterparts, in neighboring sections, AChE-poor striosomes. We conclude that during development muscarinic cholinergic function is compartmentalized in the striatum in association with dopamine-containing afferents, and that this compartmentalization may persist to some degree in the adult.
ESTHER : Nastuk_1985_J.Comp.Neurol_237_176
PubMedSearch : Nastuk_1985_J.Comp.Neurol_237_176
PubMedID: 4031121

Title : Correspondence between the dopamine islands and striosomes of the mammalian striatum - Graybiel_1984_Neurosci_13_1157
Author(s) : Graybiel AM
Ref : Neuroscience , 13 :1157 , 1984
Abstract : During the development of the mammalian striatum, the early-forming dopamine innervation is broken up into macroscopic patches called "dopamine islands". These express high tyrosine hydroxylase-like immunoreactivity and are also rich in acetylcholinesterase activity. The mature striatum has prominent macroscopic compartments called "striosomes" that were first characterized by their low acetylcholinesterase activity and since have been related to heterogeneities in striatal input-output organizations. This report describes two sets of experiments designed to determine the relationship between the dopamine islands and the striosomes. The distributions of striatal tyrosine hydroxylase-like immunoreactivity and acetylcholinesterase activity were first compared in a series of kittens and young cats ranging in age from 1-228 postnatal days. During this time, the pattern of tyrosine hydroxylase-like immunoreactivity changed from islandic (patchy) to diffuse, and the pattern of acetylcholinesterase staining changed from one of acetylcholinesterase-rich patches to one of acetylcholinesterase-poor striosomes. The dopamine islands were in register with the acetylcholinesterase-poor patches at early developmental stages and at later stages the islands matched striosomes. These observations establish a correspondence between the dopamine islands and striosomes and demonstrate that the acetylcholinesterase-rich patches of the immature caudate nucleus become the acetylcholinesterase-poor striosomes of the adult. In a second set of experiments, cat fetuses were exposed to [3H]thymidine at embryonic days 22-29 in order to label the clustered subpopulations of striatal neurons known from previous experiments to lie in striosomes [Graybiel and Hickey (1982) Proc. natn. Acad. Sci. U.S.A. 79, 198-202]. The [3H]thymidine-labeled brains were examined at late fetal (embryonic days 50-52), early postnatal (days 1-21) and later postnatal (days 62-199) ages. The clusters of [3H]thymidine-labeled neurons were aligned with tyrosine hydroxylase-rich, acetylcholinesterase-rich patches early in development, and with acetylcholinesterase-poor striosomes at later stages. There were marked dorsoventral differences in the intensity of tyrosine hydroxylase-like immunoreactivity in the dopamine islands and this was confirmed in neonatal rats. A "dorsal islandic system" was defined as having crisp, highly immunoreactive islands; ventrally, regions of low and medium tyrosine hydroxylase-like immunoreactivity formed a mosaic.(ABSTRACT TRUNCATED AT 400 WORDS)
ESTHER : Graybiel_1984_Neurosci_13_1157
PubMedSearch : Graybiel_1984_Neurosci_13_1157
PubMedID: 6152035

Title : Neurochemically specified subsystems in the basal ganglia - Graybiel_1984_Ciba.Found.Symp_107_114
Author(s) : Graybiel AM
Ref : Ciba Found Symp , 107 :114 , 1984
Abstract : The fibre pathways associated with the basal ganglia include through-conduction lines and side-loops associated with the striatum, pallidum and substantia nigra. Each of these regions is now known to contain subdivisions differing from one another in the neurotransmitter-related compounds they contain. This paper includes an outline of these new findings and a commentary on some of their functional implications.
ESTHER : Graybiel_1984_Ciba.Found.Symp_107_114
PubMedSearch : Graybiel_1984_Ciba.Found.Symp_107_114
PubMedID: 6149896

Title : Compartmental distribution of striatal cell bodies expressing [Met]enkephalin-like immunoreactivity - Graybiel_1984_Proc.Natl.Acad.Sci.U.S.A_81_7980
Author(s) : Graybiel AM , Chesselet MF
Ref : Proc Natl Acad Sci U S A , 81 :7980 , 1984
Abstract : Striatal cell bodies and fibers expressing [Met]enkephalin [( Met]Enk)-like immunoreactivity were studied with two variants of the peroxidase-antiperoxidase method in normal primates and cats and in cats pretreated with colchicine. Strikingly different patterns of [Met]Enk-like immunoreactivity were observed, both in fiber and cell body immunostaining, depending on the technical protocols followed; no single histochemical protocol fully revealed the compartmentalization present. In the dorsal striatum, patches of [Met]Enk-positive neuropil, known to line up with the acetylcholinesterase-poor striatal zones called striosomes, appeared in sections treated by protocols favoring fiber immunostaining. In sections stained by procedures favoring perikaryal staining, the striosomes appeared as Enk-poor patches in a field of immunoreactive cells and neuropil. When cell-body staining was enhanced by pretreatment with colchicine, cells expressing [Met]Enk-like immunoreactivity appeared both in and out of striosomes, and the striosomal neuropil appeared Enk-rich. These results suggest that there are subtypes of Enk-positive neurons in the striatum, including a "colchicine-dependent subtype" in dorsal striosomes, and suggest that the Enk-positive striatal neuropil is also made up of different components. Immunospecificity of this dorsal striosomal system was further demonstrated by the finding that neurons expressing intense immunoreactivity to substance P and to dynorphin B were largely confined to striosomes.
ESTHER : Graybiel_1984_Proc.Natl.Acad.Sci.U.S.A_81_7980
PubMedSearch : Graybiel_1984_Proc.Natl.Acad.Sci.U.S.A_81_7980
PubMedID: 6440146

Title : Organization of the striate-recipient zone of the cats lateralis posterior-pulvinar complex and its relations with the geniculostriate system - Berson_1983_Neurosci_9_337
Author(s) : Berson DM , Graybiel AM
Ref : Neuroscience , 9 :337 , 1983
Abstract : The extrageniculate visual thalamus of the cat is divisible into several major subdivisions but only one receives dense fiber projections from the striate cortex. In the present study, modern axon transport techniques and acetylcholinesterase histochemistry were used to examine the internal organization of this striate-recipient zone and some of its afferent and efferent connections. A detailed study of the corticothalamic fiber projections of the striate cortex clarified the topographic organization and boundaries of the striate-recipient zone. The nature and course of "projection lines" within the zone were defined and the subdivision was shown to correspond closely to a region of relatively weak acetylcholinesterase staining. Corticothalamic projections from two regions of the extrastriate visual cortex, area 19 and the medial division of the Clare-Bishop complex, converge with those from area 17 in the striate-recipient zone, but these extrastriate areas have more widespread projections to the extrageniculate thalamus than does the striate cortex. A weak subcortical projection to the striate-recipient zone was demonstrated, apparently originating in the superior colliculus. Retrograde tracing experiments indicated that the corticothalamic inputs of the striate-recipient zone are precisely reciprocal by thalamocortical projections. Extrageniculate thalamic projections to area 17 arise exclusively from this thalamic subdivision and are highly topographically ordered. The striate-recipient zone projects massively and apparently retinotopically to area 19 and to the medial division of the Clarc-Bishop area, as well as area 21(a), but these extrastriate areas receive additional afferents from other subdivisions of the extrageniculate thalamus. These findings appear to rule out a "non-specific" functional role for the striate-recipient zone. In its topographic organization, its reciprocal connections with areas of the visual cortex, and its sheer volume, the zone seems comparable to the dorsal lateral geniculate nucleus and may be fairly considered a satellite of the geniculocortical system. Certain of the zone's organizational and connectional features may be clues to its functional role and its possible homologues in other mammalian forms.
ESTHER : Berson_1983_Neurosci_9_337
PubMedSearch : Berson_1983_Neurosci_9_337
PubMedID: 6877598

Title : Compartmental organization of the mammalian striatum -
Author(s) : Graybiel AM
Ref : Prog Brain Res , 58 :247 , 1983
PubMedID: 6635191

Title : Chemospecificity of ontogenetic units in the striatum: demonstration by combining [3H]thymidine neuronography and histochemical staining - Graybiel_1982_Proc.Natl.Acad.Sci.U.S.A_79_198
Author(s) : Graybiel AM , Hickey TL
Ref : Proc Natl Acad Sci U S A , 79 :198 , 1982
Abstract : Neurons being generated in the striatum of 10 fetal cats were pulse labeled by injection of [3H]thymidine directly into the maternal uterus at times ranging between the 22nd and 30th days (E22-E30) of the 65-day gestational period. Many of the striatal neurons labeled during this interval were found, at adolescence, to form 100- to 600-mum-wide cell clusters in the caudate nucleus. In E24-E30 specimens, we compared the distributions of these cell clusters with the locations of patches of low acetylcholinesterase activity and high enkephalin immunoreactivity (the "striosomes') visualized in serially adjoining sections. We found precise matches between most of the cell clusters and the acetylcholinesterase-poor enkephalin-rich zones, regardless of the embryonic age at which exposure to the [3H]thymidine had occurred. We conclude that the histochemically distinct striosomal patch-works observed in the acetylcholinesterase and enkephalin preparations correspond to ontogenetic units of the striatum.
ESTHER : Graybiel_1982_Proc.Natl.Acad.Sci.U.S.A_79_198
PubMedSearch : Graybiel_1982_Proc.Natl.Acad.Sci.U.S.A_79_198
PubMedID: 6172791

Title : Pseudocholinesterase staining in the primary visual pathway of the macaque monkey -
Author(s) : Graybiel AM , Ragsdale CW, Jr.
Ref : Nature , 299 :439 , 1982
PubMedID: 7121580

Title : The fronto-striatal projection in the cat and monkey and its relationship to inhomogeneities established by acetylcholinesterase histochemistry - Ragsdale_1981_Brain.Res_208_259
Author(s) : Ragsdale CW, Jr. , Graybiel AM
Ref : Brain Research , 208 :259 , 1981
Abstract : The distribution of cortico-striatal fibers from the frontal cortex was studied by autoradiography in cat and monkey and compared with the patterns of striatal acetylcholinesterase activity observed in the same brains. The clustering patterns of labeled fronto-caudate fibers were found to correspond to a large extent to the inhomogeneities in enzyme activity identified by the acetylthiocholinesterase staining method.
ESTHER : Ragsdale_1981_Brain.Res_208_259
PubMedSearch : Ragsdale_1981_Brain.Res_208_259
PubMedID: 6163506

Title : Direct demonstration of a correspondence between the dopamine islands and acetylcholinesterase patches in the developing striatum - Graybiel_1981_Proc.Natl.Acad.Sci.U.S.A_78_5871
Author(s) : Graybiel AM , Pickel VM , Joh TH , Reis DJ , Ragsdale CW, Jr.
Ref : Proc Natl Acad Sci U S A , 78 :5871 , 1981
Abstract : The distribution of dopamine-containing processes in the striatum of fetal and neonatal cats was studied by immunohistochemical and glyoxylic acid histofluorescence methods and compared to the distribution of acetylcholinesterase (acetylcholine acetylhydrolase, EC observed by thiocholine histochemistry in the same or serially adjoining sections. Both methods for demonstrating the dopamine innervation revealed the characteristic patchwork of dopamine "islands" in the caudoputamen, in which catecholamine histofluorescence or tyrosine hydroxylase [tyrosine 3-monooxygenase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC]-like immunoreactivity was concentrated into 0.2- to 0.6-mm-wide patches. Both methods also demonstrated a high degree of patterning of the dopamine innervation in the ventral striatum, including the nucleus accumbens septi. A detailed and striking match was found between these configurations and the compartmental distribution of acetylcholinesterase observed in the caudoputamen and ventral striatum of the same brains. The correspondence between the dopamine and acetylcholinesterase figures was most obvious in the fetal brains, in which the background acetylcholinesterase staining was lightest, but matches between the dopamine islands and acetylcholinesterase patches could still be seen in the kittens. There was no clear alignment of striatal cell bodies stained for acetylcholinesterase with either the dopamine or the acetylcholinesterase-positive patches. Nor was there an obvious correspondence between dopamine and acetylcholinesterase in the striatal background matrix. We conclude that, at least during ontogenesis, it is the clustered arrangements of dopamine and acetylcholinesterase that are, in particular, tightly linked, and we suggest that information about the maturation of these clusters may be crucial in assessing the functions of striatal dopamine and acetylcholinesterase in the adult.
ESTHER : Graybiel_1981_Proc.Natl.Acad.Sci.U.S.A_78_5871
PubMedSearch : Graybiel_1981_Proc.Natl.Acad.Sci.U.S.A_78_5871
PubMedID: 6117860

Title : An immunohistochemical study of enkephalins and other neuropeptides in the striatum of the cat with evidence that the opiate peptides are arranged to form mosaic patterns in register with the striosomal compartments visible by acetylcholinesterase staining -
Author(s) : Graybiel AM , Ragsdale CW, Jr. , Yoneoka ES , Elde RP
Ref : Neuroscience , 6 :377 , 1981
PubMedID: 6164013

Title : Autoradiographic evidence for a projection from the pretectal nucleus of the optic tract to the dorsal lateral geniculate complex in the cat - Graybiel_1980_Brain.Res_195_1
Author(s) : Graybiel AM , Berson DM
Ref : Brain Research , 195 :1 , 1980
Abstract : A pathway from the pretectal region to the dorsal division of the lateral geniculate body has been studied by autoradiography in adult cats following injection of tritium-labeled amino acids into the meso-diencephalic border zone. The findings suggest that the pretecto-geniculate connection arises in the ipsilateral nucleus of the optic tract (NOT) and terminates in the principle dorsal layers of the geniculate body (A and A1), in lamina C and most massively in the medial interlaminar nucleus. In the A layers and lamina C, the pretectal fibers from a relatively even matting with partial interruptions occurring at the interlaminar leaflets. The ventral C layers do not appear to receive a substantial pretectal input as they were only weakly labeled, and partly in a perforant fiber pattern, after injections confined to the pretectum. Topographic ordering of the projection was evident at least along the medial to lateral axis of the NOT, fibers from the medial part terminating caudally, and those from the lateral part rostrally, within the lateral geniculate complex. The laminar pattern of termination correlates closely with the distribution of retinal Y-cell input and acetylcholinesterase activity in the geniculate body but contrasts sharply with the pattern of termination of tecto-geniculate fibers. Of potential importance in considering the functional significance of the pretecto-geniculate pathway is the fact that the NOT has been implicated in the mechanism of optokinetic nystagmus and the fact that the pathway terminates within the layers of the lateral geniculate body known to provide the main geniculo-cortical input to layer IV of the striate cortex.
ESTHER : Graybiel_1980_Brain.Res_195_1
PubMedSearch : Graybiel_1980_Brain.Res_195_1
PubMedID: 7397490

Title : Histochemical identification and afferent connections of subdivisions in the lateralis posterior-pulvinar complex and related thalamic nuclei in the cat -
Author(s) : Graybiel AM , Berson DM
Ref : Neuroscience , 5 :1175 , 1980
PubMedID: 7402466

Title : Clumping of acetylcholinesterase activity in the developing striatum of the human fetus and young infant - Graybiel_1980_Proc.Natl.Acad.Sci.U.S.A_77_1214
Author(s) : Graybiel AM , Ragsdale CW, Jr.
Ref : Proc Natl Acad Sci U S A , 77 :1214 , 1980
Abstract : The distribution of acetylcholinesterase activity (acetylcholine acetylhydrolase, EC in the developing human striatum has been studied histochemically in autopsy material from fetal brains of estimated gestational ages 16-29 weeks (180-1000 g) and from the brains of infants 2 days to 4 months old. The findings provide evidence that striatal acetylcholinesterase activity in the human fetus and neonate is concentrated in a network of densely stained zones that appear in cross section as variably shaped 0.5- to 1.0-mm-wide dark patches distributed in a lighter background matrix. An orderly arrangement of the patches seemed well established in the putamen by the 16th-18th week of gestation (crown-rump length 14-15 cm) but in the caudate nucleus the pattern was still not fully elaborated at these ages. The lateroventral part of the caput was mainly dark and its rostromedial margin, though rich early on in pseudocholinesterase activity, was still without strong acetylcholinesterase activity as late as 20-21 weeks (crown-rump length 16-20 cm). The ganglionic eminence at these ages was sharply divided into a dorsal part with little cholinesterase activity and a ventral part with a high content of pseudocholinesterase. Little information was gained about striatal development during late stages of gestation, but in three 5- to 7-month fetal specimens not only dark patches but also patches with dark perimeters and pale centers were present. Clumping of cholinesterase activity appeared at birth and up to the third month of postnatal life. The patches in both caudate nucleus and putamen were dark and of fairly uniform tint in the striatum of the young infant and the matrix staining was darker than in the fetuses. Around the fourth postnatal month hints of the mature pattern were present, with zones of low cholinesterase activity appearing against a dark background in the caudate nucleus and (in one case) a nearly homogeneous staining pattern appearing in the putamen.
ESTHER : Graybiel_1980_Proc.Natl.Acad.Sci.U.S.A_77_1214
PubMedSearch : Graybiel_1980_Proc.Natl.Acad.Sci.U.S.A_77_1214
PubMedID: 6928671

Title : Periodic-compartmental distribution of acetylcholinesterase in the superior colliculus of the human brain -
Author(s) : Graybiel AM
Ref : Neuroscience , 4 :643 , 1979
PubMedID: 450255

Title : Compartments in the striatum of the cat observed by retrograde cell labeling - Graybiel_1979_Exp.Brain.Res_34_189
Author(s) : Graybiel AM , Ragsdale CW, Jr. , Moon Edley S
Ref : Experimental Brain Research , 34 :189 , 1979
Abstract : The distribution of neurons giving rise to striatal efferent projections has been studied in the cat by the aid of Mesulam's histochemical methods following large injections of horseradish peroxidase into the pallidum and substantia nigra. The findings suggest that neurons of medium size form a major fraction of the efferent neurons of the striatum and that these neurons are grouped into geometrically complex, three-dimensional networks.
ESTHER : Graybiel_1979_Exp.Brain.Res_34_189
PubMedSearch : Graybiel_1979_Exp.Brain.Res_34_189
PubMedID: 759226

Title : A stereometric pattern of distribution of acetylthiocholinesterase in the deep layers of the superior colliculus -
Author(s) : Graybiel AM
Ref : Nature , 272 :539 , 1978
PubMedID: 99660

Title : Histochemically distinct compartments in the striatum of human, monkeys, and cat demonstrated by acetylthiocholinesterase staining - Graybiel_1978_Proc.Natl.Acad.Sci.U.S.A_75_5723
Author(s) : Graybiel AM , Ragsdale CW, Jr.
Ref : Proc Natl Acad Sci U S A , 75 :5723 , 1978
Abstract : We here report observations on the distribution of acetylcholinesterase (acetylcholine hydrolase, EC in the striatum of the adult human, the rhesus monkey, and the cat. By the histochemical staining methods of Geneser-Jensen and Blackstad and of Karnovsky and Roots, compartments of low cholinesterase activity were identified in parts of the striatum in all three species. In frontal sections, these enzyme-poor zones appeared as a variable number of weakly stained approximately 0.5-mm-wide zones embedded in a darkly stained background. The zones varied in cross-sectional shape from round to elongated and were sometimes branched. They were most prominent in the head of the caudate nucleus. Three-dimensional reconstructions of serial sections through the caudate nucleus in the human and cat suggest that over distances of at least several millimeters, the zones of low enzyme activity form nearly continuous labyrinths.
ESTHER : Graybiel_1978_Proc.Natl.Acad.Sci.U.S.A_75_5723
PubMedSearch : Graybiel_1978_Proc.Natl.Acad.Sci.U.S.A_75_5723
PubMedID: 103101