TY - JOUR T1 - The Neuropsychiatric Disease-Associated Gene <em>cacna1c</em> Mediates Survival of Young Hippocampal Neurons JF - eneuro JO - eneuro DO - 10.1523/ENEURO.0006-16.2016 VL - 3 IS - 2 SP - ENEURO.0006-16.2016 AU - Anni S. Lee AU - Héctor De Jesús-Cortés AU - Zeeba D. Kabir AU - Whitney Knobbe AU - Madeline Orr AU - Caitlin Burgdorf AU - Paula Huntington AU - Latisha McDaniel AU - Jeremiah K. Britt AU - Franz Hoffmann AU - Daniel J. Brat AU - Anjali M. Rajadhyaksha AU - Andrew A. Pieper Y1 - 2016/03/01 UR - http://www.eneuro.org/content/3/2/ENEURO.0006-16.2016.abstract N2 - Genetic variations in CACNA1C, which encodes the Cav1.2 subunit of L-type calcium channels (LTCCs), are associated with multiple forms of neuropsychiatric disease that manifest high anxiety in patients. In parallel, mice harboring forebrain-specific conditional knockout of cacna1c (forebrain-Cav1.2 cKO) display unusually high anxiety-like behavior. LTCCs in general, including the Cav1.3 subunit, have been shown to mediate differentiation of neural precursor cells (NPCs). However, it has not previously been determined whether Cav1.2 affects postnatal hippocampal neurogenesis in vivo. Here, we show that forebrain-Cav1.2 cKO mice exhibit enhanced cell death of young hippocampal neurons, with no change in NPC proliferation, hippocampal size, dentate gyrus thickness, or corticosterone levels compared with wild-type littermates. These mice also exhibit deficits in brain levels of brain-derived neurotrophic factor (BDNF), and Cre recombinase-mediated knockdown of adult hippocampal Cav1.2 recapitulates the deficit in young hippocampal neurons survival. Treatment of forebrain-Cav1.2 cKO mice with the neuroprotective agent P7C3-A20 restored the net magnitude of postnatal hippocampal neurogenesis to wild-type levels without ameliorating their deficit in BDNF expression. The role of Cav1.2 in young hippocampal neurons survival may provide new approaches for understanding and treating neuropsychiatric disease associated with aberrations in CACNA1C.Visual Abstract ER -