Deficiency of Dgcr8, a gene disrupted by the 22q11.2 microdeletion, results in altered short-term plasticity in the prefrontal cortex

Karine Fénelon, Jun Mukai, Bin Xu, Pei Ken Hsu, Liam J. Drew, Maria Karayiorgou, Gerald D. Fischbach, Amy B. MacDermott, Joseph A. Gogos

Research output: Contribution to journalArticle

137 Scopus citations

Abstract

Individuals with 22q11.2 microdeletions have cognitive and behavioral impairments and the highest known genetic risk for developing schizophrenia. One gene disrupted by the 22q11.2 microdeletion is DGCR8, a component of the "microprocessor" complex that is essential for microRNA production, resulting in abnormal processing of specific brain miRNAs and working memory deficits. Here, we determine the effect of Dgcr8 deficiency on the structure and function of cortical circuits by assessing their laminar organization, as well as the neuronal morphology, and intrinsic and synaptic properties of layer 5 pyramidal neurons in the prefrontal cortex of Dgcr8+/- mutant mice. We found that heterozygous Dgcr8 mutant mice have slightly fewer cortical layer 2/4 neurons and that the basal dendrites of layer 5 pyramidal neurons have slightly smaller spines. In addition to the modest structural changes, field potential and whole-cell electrophysiological recordings performed in layer 5 of the prefrontal cortex revealed greater short-term synaptic depression during brief stimulation trains applied at 50 Hz to superficial cortical layers. This finding was accompanied by a decrease in the initial phase of synaptic potentiation. Our results identify altered short-term plasticity as a neural substrate underlying the cognitive dysfunction and the increased risk for schizophrenia associated with the 22q11.2 microdeletions.

Original languageEnglish (US)
Pages (from-to)4447-4452
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number11
DOIs
StatePublished - Mar 15 2011

Keywords

  • 22q11.2 deletion syndrome
  • Field EPSP
  • Neurogenesis
  • Patch clamp
  • Synaptic plasticity

ASJC Scopus subject areas

  • General

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