Cav3.1 t-type calcium channel is critical for cell proliferation and survival in newly generated cells of the adult hippocampus

Yasushi Yabuki, Kazuya Matsuo, Mengze Yu, Jing Xu, Kenji Sakimura, Norifumi Shioda, Kohji Fukunaga

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Aims: Adult hippocampal neurogenesis plays an important role in neuronal plasticity and maintenance in mammals. Low-threshold voltage-gated T-type calcium channels produce calcium spikes that increase fast action potentials in newborn cells in the hippocampal dentate gyrus (DG); however, their role in adult hippocampal neurogenesis remains unclear. Here, we demonstrate impaired adult hippocampal neurogenesis in Cav3.1T-type calcium channel knockout mice. Methods and Results: Cav3.1T-type calcium channel was predominantly localized in neuronal progenitor cells of the mouse hippocampal DG. By counting the number of 5-bromo-2′-deoxyuridine-labeled cells, decreased proliferation and survival of newly generated cells were observed in the adult hippocampal DG in Cav3.1 knockout mice as compared to wild-type (WT) mice. Moreover, the degree of maturation of doublecortin-positive cells in Cav3.1 knockout mice was lower than that in WT mice, suggesting that Cav3.1 deletion may impair neuronal differentiation. Consistent with impaired hippocampal neurogenesis, Cav3.1 knockout mice showed decreased social interaction. Reduced phosphorylation levels of calcium/calmodulin-dependent protein kinase II and protein kinase B were closely associated with impaired hippocampal neurogenesis in Cav3.1 knockout mice. Moreover, the mRNA and protein expression levels of brain-derived neurotrophic factor, important for neurogenesis, were significantly decreased in Cav3.1 knockout mice. Finally, gene ontology analysis revealed alterations in genes related to the promotion of cell death/apoptosis and suppression of cell proliferation/neuronal differentiation pathways, including Bdnf. Conclusion: These results suggest that the Cav3.1T-type calcium channel may be a key molecule required for cell proliferation, survival and neuronal differentiation in newly generated cells of the adult mouse hippocampus.

Original languageEnglish
Article numbere13613
JournalActa Physiologica
Issue number1
Publication statusPublished - 2021 May
Externally publishedYes


  • Cav3.1
  • T-type calcium channel
  • adult hippocampal neurogenesis
  • brain-derived neurotrophic factor
  • cell proliferation
  • cell survival

ASJC Scopus subject areas

  • Physiology


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