title: Neurexin dysfunction in adult neurons results in autistic-like behavior in mice.
abstract: Autism spectrum disorders (ASDs) comprise a group of clinical phenotypes characterized by repetitive behavior and social and communication deficits. Autism is generally viewed as a neurodevelopmental disorder where insults during embryonic or early postnatal periods result in aberrant wiring and function of neuronal circuits. Neurexins are synaptic proteins associated with autism. Here, we generated transgenic βNrx1ΔC mice in which neurexin function is selectively impaired during late postnatal stages. Whole-cell recordings in cortical neurons show an impairment of glutamatergic synaptic transmission in the βNrx1ΔC mice. Importantly, mutant mice exhibit autism-related symptoms, such as increased self-grooming, deficits in social interactions, and altered interaction for nonsocial olfactory cues. The autistic-like phenotype of βNrx1ΔC mice can be reversed after removing the mutant protein in aged animals. The defects resulting from disruption of neurexin function after the completion of embryonic and early postnatal development suggest that functional impairment of mature circuits can trigger autism-related phenotypes.
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla and Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, Campus del Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot s/n, Sevilla 41013, Spain.
authors.forename: Luis G
authors.initials: LG
authors.lastname: Rabaneda
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla and Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, Campus del Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot s/n, Sevilla 41013, Spain.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Robles-Lanuza
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla and Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, Campus del Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot s/n, Sevilla 41013, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Campus del Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot s/n, Sevilla 41013, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Nieto-González
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla and Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, Campus del Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot s/n, Sevilla 41013, Spain. Electronic address: fgs@us.es.
authors.forename: Francisco G
authors.initials: FG
authors.lastname: Scholl
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D002135:Calcium-Binding Proteins; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development / Q000378:metabolism / Q000503:physiopathology; D006120:Grooming; D053444:Inhibitory Postsynaptic Potentials; D051379:Mice; D009154:Mutation; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D010641:Phenotype; D012919:Social Behavior
chemical_list: D002135:Calcium-Binding Proteins; D019006:Neural Cell Adhesion Molecules; C527193:Nrxn1 protein, mouse