In:
Hippocampus, Wiley, Vol. 28, No. 2 ( 2018-02), p. 97-107
Abstract:
In the central nervous system, Ca V 1.2 and Ca V 1 . 3 constitute the main L‐type voltage‐gated calcium channels (LTCCs) coupling membrane depolarization to gene transcription. We have previously demonstrated that inducible disruption of Cav1.2 in type‐1 astrocyte‐like stem cells of the adult dentate gyrus (DG) impairs hippocampal neurogenesis in a cell‐autonomous fashion. To address the role of Cav1.3 channels (encoded by the Cacna1d gene), we here generated Tg GLAST‐CreERT2 / Cacna1d fl/fl /RCE:loxP mice which facilitate inducible deletion of Cacna1d in tandem with induction of EGFP expression in type‐1 cells, allowing tracking of recombined cells and their descendants. Neurosphere cultures derived from fluorescence‐activated cell sorting sorted Cacna1d ‐deficient ( Cacna1d ‐/‐ /EGFP) hippocampal neural precursor cells (NPCs) exhibited a significant decrease in proliferative activity. Further, under differentiation conditions, Cacna1d deficiency conferred an increase in astrogenesis at the expense of neurogenesis. In like manner, type‐1 cells lacking Cacna1d showed reduced proliferation in the dentate gyrus (DG) in vivo. Moreover, Cacna1d deficiency resulted in a significant decrease in the number of newly born cells adopting a neuronal fate. Finally, massive excitation induced by repeated electroconvulsive seizures rescued the proliferation defect of Cacna1d ‐/‐ /EGFP type‐1 cells. Together, the effects of Cacna1d gene deletion closely recapitulate our earlier findings on the role of Cav1.2 channels expressed by type‐1 cells. Similar to Cav1.2 channels, Cav1.3 channels on type‐1 cells boost type‐1 cell proliferation and promote subsequent neuronal fate choice.
Type of Medium:
Online Resource
ISSN:
1050-9631
,
1098-1063
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
1498049-6
