Mouse neurexin-1alpha deletion causes correlated electrophysiological and behavioral changes consistent with cognitive impairments.
Deletions in the neurexin-1alpha 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-1alpha. Hippocampal slice physiology uncovered a defect in excitatory synaptic strength in neurexin-1alpha 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-1alpha 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-1alpha deficient mice did not exhibit any obvious changes in social behaviors or in spatial learning. Together, these data indicate that the neurexin-1alpha deficiency induces a discrete neural phenotype whose extent correlates, at least in part, with impairments observed in human patients.
Etherton
Mark R
MR
Department of Molecular and Cellular Physiology, Stanford University, 1050 Arastradero Road, CA 94304, USA.
Blaiss
Cory A
CA
Powell
Craig M
CM
Südhof
Thomas C
TC
D000818:Animals; D001007:Anxiety; D001321:Autistic Disorder / Q000235:genetics; D001522:Behavior, Animal / Q000502:physiology*; D002135:Calcium-Binding Proteins; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D055724:Electrophysiological Phenomena; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D017353:Gene Deletion; D006120:Grooming / Q000502:physiology; D006624:Hippocampus / Q000502:physiology; D006801:Humans; D007858:Learning / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D009043:Motor Activity / Q000502:physiology; D019006:Neural Cell Adhesion Molecules / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D012559:Schizophrenia / Q000235:genetics; D012919:Social Behavior; D013037:Spatial Behavior / Q000502:physiology
D002135:Calcium-Binding Proteins; D019006:Neural Cell Adhesion Molecules; C527193:Nrxn1 protein, mouse