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.
Keywords
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Article info
Publication history
Published online: September 07, 2020
Accepted:
August 31,
2020
Received in revised form:
August 11,
2020
Received:
March 24,
2020
Identification
Copyright
© 2020 Society of Biological Psychiatry.
ScienceDirect
Access this article on ScienceDirectLinked Article
- “Bone” in the Brain? Osteocalcin-Expressing Neurons in Adult Hippocampus Promote Neurogenesis and Suppress AnxietyBiological PsychiatryVol. 89Issue 6
- PreviewThe ability of the dentate gyrus (DG) to generate new neurons, also known as neurogenesis, has been well established in rodents and nonhuman primates (1). How these adult-born neurons incorporate into hippocampal microcircuits and influence information processing has drawn tremendous attention over the past decade. Apart from learning and memory regulation, adult neurogenesis in the hippocampus has been proposed as a key regulator of depression and anxiety (2). A variety of rodent models for depression and anxiety (e.g., chronic social defeat, chronic immobilization, early-life stress) have exhibited impairments in neurogenesis, and similar effects are also observed in nonhuman primates (e.g., social isolation, subordination).
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