Erbb4 Deletion from Fast-Spiking Interneurons Causes Schizophrenia-like Phenotypes

Isabel delPino, Cristina García-Frigola, Nathalie Dehorter, Jorge R. Brotons-Mas, Efrén Alvarez-Salvado, María MartínezdeLagrán, Gabriele Ciceri, María Victoria Gabaldón, David Moratal, Mara Dierssen, Santiago Canals, Oscar Marín*, Beatriz Rico

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

226 Citations (Scopus)

Abstract

Genetic variation in neuregulin and its ErbB4 receptor has been linked to schizophrenia, although little is known about how they contribute to the disease process. Here, we have examined conditional Erbb4 mouse mutants to study how disruption of specific inhibitory circuits in the cerebral cortex may cause large-scale functional deficits. We found that deletion of ErbB4 from the two main classes of fast-spiking interneurons, chandelier and basket cells, causes relatively subtle but consistent synaptic defects. Surprisingly, these relatively small wiring abnormalities boost cortical excitability, increase oscillatory activity, and disrupt synchrony across cortical regions. These functional deficits are associated with increased locomotor activity, abnormal emotional responses, and impaired social behavior and cognitive function. Our results reinforce the view that dysfunction of cortical fast-spiking interneurons might be central to the pathophysiology of schizophrenia

Original languageEnglish
Pages (from-to)1152-1168
Number of pages17
JournalNeuron
Volume79
Issue number6
DOIs
Publication statusPublished - 18 Sept 2013
Externally publishedYes

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