title: Age-Dependent Specific Changes in Area CA2 of the Hippocampus and Social Memory Deficit in a Mouse Model of the 22q11.2 Deletion Syndrome.
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.
authors.affiliation: CNRS UMR8118, Team Synaptic Plasticity and Neural Networks, Université Paris Descartes, 75006 Paris, France.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Piskorowski
authors.affiliation: CNRS UMR8118, Team Synaptic Plasticity and Neural Networks, Université Paris Descartes, 75006 Paris, France.
authors.forename: Kaoutsar
authors.initials: K
authors.lastname: Nasrallah
authors.affiliation: Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Diamantopoulou
authors.affiliation: Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Mukai
authors.affiliation: Department of Neuroscience, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Sami I
authors.initials: SI
authors.lastname: Hassan
authors.affiliation: Department of Neuroscience, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Siegelbaum
authors.affiliation: Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Department of Neuroscience, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. Electronic address: jag90@cumc.columbia.edu.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Gogos
authors.affiliation: CNRS UMR8118, Team Synaptic Plasticity and Neural Networks, Université Paris Descartes, 75006 Paris, France. Electronic address: vivien.chevaleyre@parisdescartes.fr.
authors.forename: Vivien
authors.initials: V
authors.lastname: Chevaleyre
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000375:Aging; D000818:Animals; D003072:Cognition Disorders / Q000235:genetics / Q000503:physiopathology; D004062:DiGeorge Syndrome / Q000235:genetics / Q000503:physiopathology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008568:Memory / Q000502:physiology; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D010320:Parvalbumins / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics / Q000503:physiopathology; D012919:Social Behavior
chemical_list: D010320:Parvalbumins