gabaergic control of critical developmental periods for anxiety- and depression-related behavior in micegaba ergic控制关键发展时期的焦虑和抑郁症小鼠的行为.pdfVIP

GABAergic Control of Critical Developmental Periods for Anxiety- and Depression-Related Behavior in Mice Qiuying Shen1,2,4, Thomas Fuchs1,4, Nadia Sahir1,4, Bernhard Luscher1,2,3,4* 1 Department of Biology, Pennsylvania State University, University Park, Pennsylvania, United States of America, 2 Department of Biochemistry Molecular Biology, Pennsylvania State University, University Park, Pennsylvania, United States of America, 3 Department of Psychiatry, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania, United States of America, 4 Center for Molecular Investigation of Neurological Disorders, Pennsylvania State University, University Park, Pennsylvania, United States of America Abstract Vulnerability for anxiety and depressive disorders is thought to have origins in early life and is increasingly recognized to involve deficits in GABAergic neurotransmission. Mice that were rendered heterozygous for the c2 subunit gene of GABAA receptors (GABA Rs) show behavioral, cognitive, neuroendocrine and pharmacologic features expected of a mouse model A of melancholic anxious depression, including reduced survival of adult-born hippocampal neurons. Here we embarked on elucidating the developmental substrate underlying this phenotype, focusing on the Elevated Plus Maze and Forced Swim Test as relevant behavioral paradigms. In a first series of experiments using hemizygous tamoxifen-induced genetic inactivation of a floxed c2 genomic locus we show that reducing the gene dosage at postnatal days (P)13/14 but not P27/28 results in altered behavior in both of these tests in adulthood, reminiscent of the anxious-depressive phenotype previously described for global heterozygous mice. However, in contrast to global heterozygous mice, the behavioral changes induced by c2 subunit knockdown at P13/14 oc