Neuroligin-1 deletion results in impaired spatial memory and increased repetitive behavior

Jacqueline Blundell, Cory A. Blaiss, Mark R. Etherton, Felipe Espinosa, Katsuhiko Tabuchi, Christopher Walz, Marc F. Bolliger, Thomas C. Südhof, Craig M. Powell

Research output: Contribution to journalArticle

294 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2115-2129
Number of pages15
JournalJournal of Neuroscience
Volume30
Issue number6
DOIs
StatePublished - Feb 10 2010

ASJC Scopus subject areas

  • Neuroscience(all)

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    Blundell, J., Blaiss, C. A., Etherton, M. R., Espinosa, F., Tabuchi, K., Walz, C., Bolliger, M. F., Südhof, T. C., & Powell, C. M. (2010). Neuroligin-1 deletion results in impaired spatial memory and increased repetitive behavior. Journal of Neuroscience, 30(6), 2115-2129. https://doi.org/10.1523/JNEUROSCI.4517-09.2010