Overexpression of the cell adhesion protein neuroligin-1 induces learning deficits and impairs synaptic plasticity by altering the ratio of excitation to inhibition in the hippocampus

Regina Dahlhaus, Rochelle M. Hines, Brennan D. Eadie, Timal S. Kannangara, Dustin J. Hines, Craig E. Brown, Brian R. Christie, Alaa El-Hussefini

Research output: Contribution to journalArticlepeer-review

114 Citations (Scopus)

Abstract

Trans-synaptic cell-adhesion molecules have been implicated in regulating CNS synaptogenesis. Among these, the Neuroligin (NL) family (NLs 1-4) of postsynaptic adhesion proteins has been shown to promote the development and specification of eficitatory versus inhibitory synapses. NLs form a heterophilic complex with the presynaptic transmembrane protein Neurexin (NRX). A differential association of NLs with postsynaptic scaffolding proteins and NRX isoforms has been suggested to regulate the ratio of eficitatory to inhibitory synapses (E/I ratio). Using transgenic mice, we have tested this hypothesis by overexpressing NL1 in vivo to determine whether the relative levels of these cell adhesion molecules may influence synapse maturation, long-term potentiation (LTP), and/or learning. We found that NL1-overexpressing mice show significant deficits in memory acquisition, but not in memory retrieval. Golgi and electron microscopy analysis revealed changes in synapse morphology indicative of increased maturation of eficitatory synapses. In parallel, electrophysiological examination indicated a shift in the synaptic activity toward increased eficitation as well as impairment in LTP induction. Our results demonstrate that altered balance in the expression of molecules necessary for synapse specification and development (such as NL1) can lead to defects in memory formation and synaptic plasticity and outline the importance of rigidly controlled synaptic maturation processes.

Original languageEnglish
Pages (from-to)305-322
Number of pages18
JournalHippocampus
Volume20
Issue number2
DOIs
Publication statusPublished - Feb 2010
Externally publishedYes

ASJC Scopus Subject Areas

  • Cognitive Neuroscience

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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