Mouse neurexin-1α deletion causes correlated electrophysiological and behavioral changes consistent with cognitive impairments

Mark R. Etherton, Cory A. Blaiss, Craig M. Powell, Thomas C. Südhof

Research output: Contribution to journalArticle

248 Citations (Scopus)

Abstract

Deletions in the neurexin-1α gene were identified in large-scale unbiased screens for copy-number variations in patients with autism or schizophrenia. To explore the underlying biology, we studied the electrophysiological and behavioral phenotype of mice lacking neurexin-1α. Hippocampal slice physiology uncovered a defect in excitatory synaptic strength in neurexin-1α deficient mice, as revealed by a decrease in miniature excitatory postsynaptic current (EPSC) frequency and in the input-output relation of evoked postsynaptic potentials. This defect was specific for excitatory synaptic transmission, because no change in inhibitory synaptic transmission was observed in the hippocampus. Behavioral studies revealed that, compared with littermate control mice, neurexin-1α deficient mice displayed a decrease in prepulse inhibition, an increase in grooming behaviors, an impairment in nest-building activity, and an improvement in motor learning. However, neurexin-1α deficient mice did not exhibit any obvious changes in social behaviors or in spatial learning. Together, these data indicate that the neurexin-1α deficiency induces a discrete neural phenotype whose extent correlates, at least in part, with impairments observed in human patients.

Original languageEnglish (US)
Pages (from-to)17998-18003
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number42
DOIs
StatePublished - Oct 20 2009

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Synaptic Transmission
Phenotype
Grooming
Synaptic Potentials
Social Behavior
Excitatory Postsynaptic Potentials
Autistic Disorder
Evoked Potentials
Hippocampus
Schizophrenia
Learning
Cognitive Dysfunction
Mouse Nrxn1 protein
Genes
Prepulse Inhibition
Spatial Learning

Keywords

  • Autism
  • Neuroligin
  • Schizophrenia
  • Synapse
  • Synaptic cell-adhesion

ASJC Scopus subject areas

  • General

Cite this

Mouse neurexin-1α deletion causes correlated electrophysiological and behavioral changes consistent with cognitive impairments. / Etherton, Mark R.; Blaiss, Cory A.; Powell, Craig M.; Südhof, Thomas C.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 42, 20.10.2009, p. 17998-18003.

Research output: Contribution to journalArticle

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