Age-Dependent Specific Changes in Area CA2 of the Hippocampus and Social Memory Deficit in a Mouse Model of the 22q11.2 Deletion Syndrome

Rebecca A. Piskorowski, Kaoutsar Nasrallah, Anastasia Diamantopoulou, Jun Mukai, Sami I. Hassan, Steven A. Siegelbaum, Joseph A. Gogos, Vivien Chevaleyre

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

Several neuropsychiatric disorders are associated with cognitive and social dysfunction. Postmortem studies of patients with schizophrenia have revealed specific changes in area CA2, a long-overlooked region of the hippocampus recently found to be critical for social memory formation. To examine how area CA2 is altered in psychiatric illness, we used the Df(16)A+/- mouse model of the 22q11.2 microdeletion, a genetic risk factor for developing several neuropsychiatric disorders, including schizophrenia. We report several age-dependent CA2 alterations: a decrease in the density of parvalbumin-expressing interneurons, a reduction in the amount of feedforward inhibition, and a change in CA2 pyramidal-neuron intrinsic properties. Furthermore, we found that area CA2 is less plastic in Df(16)A+/- mice, making it nearly impossible to evoke action potential firing in CA2 pyramidal neurons. Finally, we show that Df(16)A+/- mice display impaired social cognition, providing a potential mechanism and a neural substrate for this impairment in psychiatric disorders.

Original languageEnglish (US)
Pages (from-to)163-176
Number of pages14
JournalNeuron
Volume89
Issue number1
DOIs
StatePublished - Jan 6 2016
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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