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.

中文翻译：

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胚胎出生的背齿状颗粒神经元对 BDNF、成人海马神经发生和抗焦虑样行为的活动依赖性增加的关键作用

背景技术齿状回(DG)是控制信息流入海马体的“门”，在调节认知(例如，空间学习和记忆)和情绪行为中起重要作用。DG 神经元的缺陷不仅会导致神经系统疾病，而且会导致精神疾病，例如焦虑症。虽然 DG 在空间学习和记忆中的功能已被广泛研究，但其在调节焦虑中的作用仍然难以捉摸。方法 使用 c-Fos 标记 DG 神经元激活，我们鉴定了一组胚胎出生的背侧 DG (dDG) 神经元，它们被焦虑刺激激活并特异性表达骨钙素 (Ocn)-Cre。我们通过结合化学遗传学、电生理学、和 RNA 测序方法。结果 Ocn-Cre+ dDG 神经元对焦虑环境的反应非常活跃，但与 Ocn-Cre 或成人出生的 dDG 神经元相比，其兴奋性较低且突触前输入较少。激活 Ocn-Cre+ dDG 神经元会抑制焦虑样行为并增加成人 DG 神经发生，而消融或长期抑制 Ocn-Cre+ dDG 神经元会加剧焦虑样行为、损害成人 DG 神经发生和消除活动（例如，自愿轮跑）诱导抗焦虑作用和成人 DG 神经发生。对由 Ocn-Cre+ dDG 神经元激活诱导的因子的 RNA 测序筛选确定了 BDNF，这是 Ocn-Cre+ dDG 神经元介导的抗焦虑样行为和成人 DG 神经发生所必需的。