Blundell J

References (4)

Title : Neuroligin-1 deletion results in impaired spatial memory and increased repetitive behavior - Blundell_2010_J.Neurosci_30_2115
Author(s) : Blundell J , Blaiss CA , Etherton MR , Espinosa F , Tabuchi K , Walz C , Bolliger MF , Sudhof TC , Powell CM
Ref : Journal of Neuroscience , 30 :2115 , 2010
Abstract : Neuroligins (NLs) are a family of neural cell-adhesion molecules that are involved in excitatory/inhibitory synapse specification. Multiple members of the NL family (including NL1) and their binding partners have been linked to cases of human autism and mental retardation. We have now characterized NL1-deficient mice in autism- and mental retardation-relevant behavioral tasks. NL1 knock-out (KO) mice display deficits in spatial learning and memory that correlate with impaired hippocampal long-term potentiation. In addition, NL1 KO mice exhibit a dramatic increase in repetitive, stereotyped grooming behavior, a potential autism-relevant abnormality. This repetitive grooming abnormality in NL1 KO mice is associated with a reduced NMDA/AMPA ratio at corticostriatal synapses. Interestingly, we further demonstrate that the increased repetitive grooming phenotype can be rescued in adult mice by administration of the NMDA receptor partial coagonist d-cycloserine. Broadly, these data are consistent with a role of synaptic cell-adhesion molecules in general, and NL1 in particular, in autism and implicate reduced excitatory synaptic transmission as a potential mechanism and treatment target for repetitive behavioral abnormalities.
ESTHER : Blundell_2010_J.Neurosci_30_2115
PubMedSearch : Blundell_2010_J.Neurosci_30_2115
PubMedID: 20147539

Title : Increased anxiety-like behavior in mice lacking the inhibitory synapse cell adhesion molecule neuroligin 2 - Blundell_2009_Genes.Brain.Behav_8_114
Author(s) : Blundell J , Tabuchi K , Bolliger MF , Blaiss CA , Brose N , Liu X , Sudhof TC , Powell CM
Ref : Genes Brain Behav , 8 :114 , 2009
Abstract : Neuroligins (NL) are postsynaptic cell adhesion molecules that are thought to specify synapse properties. Previous studies showed that mutant mice carrying an autism-associated point mutation in NL3 exhibit social interaction deficits, enhanced inhibitory synaptic function and increased staining of inhibitory synaptic puncta without changes in overall inhibitory synapse numbers. In contrast, mutant mice lacking NL2 displayed decreased inhibitory synaptic function. These studies raised two relevant questions. First, does NL2 deletion impair inhibitory synaptic function by altering the number of inhibitory synapses, or by changing their efficacy? Second, does this effect of NL2 deletion on inhibition produce behavioral changes? We now show that although NL2-deficient mice exhibit an apparent decrease in number of inhibitory synaptic puncta, the number of symmetric synapses as determined by electron microscopy is unaltered, suggesting that NL2 deletion impairs the function of inhibitory synapses without decreasing their numbers. This decrease in inhibitory synaptic function in NL2-deficient mice correlates with a discrete behavioral phenotype that includes a marked increase in anxiety-like behavior, a decrease in pain sensitivity and a slight decrease in motor co-ordination. This work confirms that NL2 modulates inhibitory synaptic function and is the first demonstration that global deletion of NL2 can lead to a selective behavioral phenotype.
ESTHER : Blundell_2009_Genes.Brain.Behav_8_114
PubMedSearch : Blundell_2009_Genes.Brain.Behav_8_114
PubMedID: 19016888

Title : The role of the read through variant of acetylcholinesterase in anxiogenic effects of predator stress in mice - Adamec_2008_Behav.Brain.Res_189_180
Author(s) : Adamec R , Head D , Soreq H , Blundell J
Ref : Behavioural Brain Research , 189 :180 , 2008
Abstract : This study examined the role of the read through variant of acetylcholinesterase (AChE-R) in lasting changes in murine affective behavior produced by a brief predator stress. AChE-R is elevated by stress in limbic cholinergic circuits implicated in anxiogenic effects of predator stress. The expression of AChE-R was blocked with a systemically administered central acting antisense oligonucleotide for AChE-R (EN101). EN101 was injected at multiple points prior to and after a predator stress in male C57 mice. Seven days after the last injection, behavior was tested. Predator stress caused a significant increase in startle amplitude, which EN101 blocked. This effect was specific to EN101, as the negative control inactive form of EN101, INVEN101 was without effect on stress effects on startle. Neither EN101 nor INVEN101 altered the anxiogenic effects of predator stress on behavior in the elevated plus maze, and both drugs partially reduced stress suppression of time active in the hole board. In the light dark box test, INVEN101 exhibited a weak block of stress effects on behavior for reasons which are unclear. Taken together, findings support the view that multiple neural systems are responsible for the different changes in behavior produced by predator stress. Present findings also suggest a role for AChE-R in specific anxiogenic (hyperarousal) effects following predator stress. Since AChE-R manipulations took place starting 23 h prior to predator stress and continued 48 h after predator stress, further research is necessary to determine the role of AChE-R in initiation and/or consolidation of hyperarousal effects of predator stress.
ESTHER : Adamec_2008_Behav.Brain.Res_189_180
PubMedSearch : Adamec_2008_Behav.Brain.Res_189_180
PubMedID: 18243359

Title : A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice - Tabuchi_2007_Science_318_71
Author(s) : Tabuchi K , Blundell J , Etherton MR , Hammer RE , Liu X , Powell CM , Sudhof TC
Ref : Science , 318 :71 , 2007
Abstract : Autism spectrum disorders (ASDs) are characterized by impairments in social behaviors that are sometimes coupled to specialized cognitive abilities. A small percentage of ASD patients carry mutations in genes encoding neuroligins, which are postsynaptic cell-adhesion molecules. We introduced one of these mutations into mice: the Arg451-->Cys451 (R451C) substitution in neuroligin-3. R451C mutant mice showed impaired social interactions but enhanced spatial learning abilities. Unexpectedly, these behavioral changes were accompanied by an increase in inhibitory synaptic transmission with no apparent effect on excitatory synapses. Deletion of neuroligin-3, in contrast, did not cause such changes, indicating that the R451C substitution represents a gain-of-function mutation. These data suggest that increased inhibitory synaptic transmission may contribute to human ASDs and that the R451C knockin mice may be a useful model for studying autism-related behaviors.
ESTHER : Tabuchi_2007_Science_318_71
PubMedSearch : Tabuchi_2007_Science_318_71
PubMedID: 17823315
Gene_locus related to this paper: human-NLGN3 , human-NLGN4X