Giros B

References (4)

Title : The high efficacy of muscarinic M4 receptor in D1 medium spiny neurons reverses striatal hyperdopaminergia - Nair_2019_Neuropharmacol_146_74
Author(s) : Nair AG , Castro LRV , El Khoury M , Gorgievski V , Giros B , Tzavara ET , Hellgren-Kotaleski J , Vincent P
Ref : Neuropharmacology , 146 :74 , 2019
Abstract : The opposing action of dopamine and acetylcholine has long been known to play an important role in basal ganglia physiology. However, the quantitative analysis of dopamine and acetylcholine signal interaction has been difficult to perform in the native context because the striatum comprises mainly two subtypes of medium-sized spiny neurons (MSNs) on which these neuromodulators exert different actions. We used biosensor imaging in live brain slices of dorsomedial striatum to monitor changes in intracellular cAMP at the level of individual MSNs. We observed that the muscarinic agonist oxotremorine decreases cAMP selectively in the MSN subpopulation that also expresses D1 dopamine receptors, an action mediated by the M4 muscarinic receptor. This receptor has a high efficacy on cAMP signaling and can shut down the positive cAMP response induced by dopamine, at acetylcholine concentrations which are consistent with physiological levels. This supports our prediction based on theoretical modeling that acetylcholine could exert a tonic inhibition on striatal cAMP signaling, thus supporting the possibility that a pause in acetylcholine release is required for phasic dopamine to transduce a cAMP signal in D1 MSNs. In vivo experiments with acetylcholinesterase inhibitors donepezil and tacrine, as well as with the positive allosteric modulators of M4 receptor VU0152100 and VU0010010 show that this effect is sufficient to reverse the increased locomotor activity of DAT-knockout mice. This suggests that M4 receptors could be a novel therapeutic target to treat hyperactivity disorders.
ESTHER : Nair_2019_Neuropharmacol_146_74
PubMedSearch : Nair_2019_Neuropharmacol_146_74
PubMedID: 30468798

Title : Presynaptic D2 dopamine receptors control long-term depression expression and memory processes in the temporal hippocampus - Rocchetti_2015_Biol.Psychiatry_77_513
Author(s) : Rocchetti J , Isingrini E , Dal Bo G , Sagheby S , Menegaux A , Tronche F , Levesque D , Moquin L , Gratton A , Wong TP , Rubinstein M , Giros B
Ref : Biological Psychiatry , 77 :513 , 2015
Abstract : BACKGROUND: Dysfunctional mesocorticolimbic dopamine signaling has been linked to alterations in motor and reward-based functions associated with psychiatric disorders. Converging evidence from patients with psychiatric disorders and use of antipsychotics suggests that imbalance of dopamine signaling deeply alters hippocampal functions. However, given the lack of full characterization of a functional mesohippocampal pathway, the precise role of dopamine transmission in memory deficits associated with these disorders and their dedicated therapies is unknown. In particular, the positive outcome of antipsychotic treatments, commonly antagonizing D2 dopamine receptors (D2Rs), on cognitive deficits and memory impairments remains questionable. METHODS: Following pharmacologic and genetic manipulation of dopamine transmission, we performed anatomic, neurochemical, electrophysiologic, and behavioral investigations to uncover the role of D2Rs in hippocampal-dependent plasticity and learning. Naive mice (n = 4-21) were used in the different procedures. RESULTS: Dopamine modulated both long-term potentiation and long-term depression in the temporal hippocampus as well as spatial and recognition learning and memory in mice through D2Rs. Although genetic deletion or pharmacologic blockade of D2Rs led to the loss of long-term potentiation expression, the specific genetic removal of presynaptic D2Rs impaired long-term depression and performances on spatial memory tasks. CONCLUSIONS: Presynaptic D2Rs in dopamine fibers of the temporal hippocampus tightly modulate long-term depression expression and play a major role in the regulation of hippocampal learning and memory. This direct role of mesohippocampal dopamine input as uncovered here adds a new dimension to dopamine involvement in the physiology underlying deficits associated with neuropsychiatric disorders.
ESTHER : Rocchetti_2015_Biol.Psychiatry_77_513
PubMedSearch : Rocchetti_2015_Biol.Psychiatry_77_513
PubMedID: 24742619

Title : Expression of vesicular glutamate transporters, VGLUT1 and VGLUT2, in cholinergic spinal motoneurons - Herzog_2004_Eur.J.Neurosci_20_1752
Author(s) : Herzog E , Landry M , Buhler E , Bouali-Benazzouz R , Legay C , Henderson CE , Nagy F , Dreyfus PA , Giros B , El Mestikawy S
Ref : European Journal of Neuroscience , 20 :1752 , 2004
Abstract : Mammalian spinal motoneurons are cholinergic neurons that have long been suspected to use also glutamate as a neurotransmitter. We report that VGLUT1 and VGLUT2, two subtypes of vesicular glutamate transporters, are expressed in rat spinal motoneurons. Both proteins are present in somato-dendritic compartments as well as in axon terminals in primary cultures of immunopurified motoneurons and sections of spinal cord from adult rat. However, VGLUT1 and VGLUT2 are not found at neuromuscular junctions of skeletal muscles. After intracellular injection of biocytin in motoneurons, VGLUT2 is observed in anterogradely labelled terminals contacting Renshaw inhibitory interneurons. These VGLUT2- and VGLUT1-positive terminals do not express VAChT, the vesicular acetylcholine transporter. Overall, our study establishes for the first time that (i) mammalian spinal motoneurons express vesicular glutamate transporters, (ii) these motoneurons have the potential to release glutamate (in addition to acetylcholine) at terminals contacting Renshaw cells, and finally (iii) the VGLUTs are not present at neuromuscular synapses of skeletal muscles.
ESTHER : Herzog_2004_Eur.J.Neurosci_20_1752
PubMedSearch : Herzog_2004_Eur.J.Neurosci_20_1752
PubMedID: 15379996

Title : Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism - Jamain_2003_Nat.Genet_34_27
Author(s) : Jamain S , Quach H , Betancur C , Rastam M , Colineaux C , Gillberg IC , Soderstrom H , Giros B , Leboyer M , Gillberg C , Bourgeron T
Ref : Nat Genet , 34 :27 , 2003
Abstract : Many studies have supported a genetic etiology for autism. Here we report mutations in two X-linked genes encoding neuroligins NLGN3 and NLGN4 in siblings with autism-spectrum disorders. These mutations affect cell-adhesion molecules localized at the synapse and suggest that a defect of synaptogenesis may predispose to autism.
ESTHER : Jamain_2003_Nat.Genet_34_27
PubMedSearch : Jamain_2003_Nat.Genet_34_27
PubMedID: 12669065
Gene_locus related to this paper: human-NLGN2 , human-NLGN4X , human-NLGN4Y , mouse-4neur , human-NLGN3