Critical Roles of Embryonic Born Dorsal Dentate Granule Neurons for Activity-Dependent Increases in BDNF, Adult Hippocampal Neurogenesis, and Antianxiety-like Behaviors

Dong Sun, Leena Milibari, Jin Xiu Pan, Xiao Ren, Ling Ling Yao, Yang Zhao, Chen Shen, Wen Bing Chen, Fu Lei Tang, Daehoon Lee, Jun Shi Zhang, Lin Mei, Wen Cheng Xiong

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Background: Dentate gyrus (DG), a “gate” that controls information flow into the hippocampus, plays important roles in regulating both cognitive (e.g., spatial learning and memory) and mood behaviors. Deficits in DG neurons contribute to the pathogenesis of not only neurological, but also psychiatric, disorders, such as anxiety disorder. Whereas DG's function in spatial learning and memory has been extensively investigated, its role in regulating anxiety remains elusive. Methods: Using c-Fos to mark DG neuron activation, we identified a group of embryonic born dorsal DG (dDG) neurons, which were activated by anxiogenic stimuli and specifically express osteocalcin (Ocn)-Cre. We further investigated their functions in regulating anxiety and the underlying mechanisms by using a combination of chemogenetic, electrophysiological, and RNA-sequencing methods. Results: The Ocn-Cre+ dDG neurons were highly active in response to anxiogenic environment but had lower excitability and fewer presynaptic inputs than those of Ocn-Cre or adult born dDG neurons. Activating Ocn-Cre+ dDG neurons suppressed anxiety-like behaviors and increased adult DG neurogenesis, whereas ablating or chronically inhibiting Ocn-Cre+ dDG neurons exacerbated anxiety-like behaviors, impaired adult DG neurogenesis, and abolished activity (e.g., voluntary wheel running)-induced anxiolytic effect and adult DG neurogenesis. RNA-sequencing screening for factors induced by activation of Ocn-Cre+ dDG neurons identified BDNF, which was required for Ocn-Cre+ dDG neurons mediated antianxiety-like behaviors and adult DG neurogenesis. Conclusions: These results demonstrate critical functions of Ocn-Cre+ dDG neurons in suppressing anxiety-like behaviors but promoting adult DG neurogenesis, and both functions are likely through activation of BDNF.

Original languageEnglish (US)
Pages (from-to)600-614
Number of pages15
JournalBiological Psychiatry
Volume89
Issue number6
DOIs
StatePublished - Mar 15 2021

Keywords

  • Adult born DG neurons
  • Adult hippocampal neurogenesis
  • Anxiety-like behaviors
  • BDNF
  • Embryonic born DG neurons
  • Osteocalcin-Cre

ASJC Scopus subject areas

  • Biological Psychiatry

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