RT Journal Article SR Electronic T1 The Neuropsychiatric Disease-Associated Gene cacna1c Mediates Survival of Young Hippocampal Neurons JF eneuro JO eneuro FD Society for Neuroscience SP ENEURO.0006-16.2016 DO 10.1523/ENEURO.0006-16.2016 VO 3 IS 2 A1 Lee, Anni S. A1 De Jesús-Cortés, Héctor A1 Kabir, Zeeba D. A1 Knobbe, Whitney A1 Orr, Madeline A1 Burgdorf, Caitlin A1 Huntington, Paula A1 McDaniel, Latisha A1 Britt, Jeremiah K. A1 Hoffmann, Franz A1 Brat, Daniel J. A1 Rajadhyaksha, Anjali M. A1 Pieper, Andrew A. YR 2016 UL http://www.eneuro.org/content/3/2/ENEURO.0006-16.2016.abstract AB 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