Adult hippocampal neurogenesis plays a critical role in memory and emotion processing, and this process is dynamically regulated by neural circuit activity. However, it remains unknown whether manipulation of neural circuit activity can achieve sufficient neurogenic effects to modulate behavior. Here we report that chronic patterned optogenetic stimulation of supramammillary nucleus (SuM) neurons in the mouse hypothalamus robustly promotes neurogenesis at multiple stages, leading to increased production of neural stem cells and behaviorally relevant adult-born neurons (ABNs) with enhanced maturity. Functionally, selective manipulation of the activity of these SuM-promoted ABNs modulates memory retrieval and anxiety-like behaviors. Furthermore, we show that SuM neurons are highly responsive to environmental novelty (EN) and are required for EN-induced enhancement of neurogenesis. Moreover, SuM is required for ABN activity-dependent behavioral modulation under a novel environment. Our study identifies a key hypothalamic circuit that couples novelty signals to the production and maturation of ABNs, and highlights the activity-dependent contribution of circuit-modified ABNs in behavioral regulation.

成人海马神经发生在记忆和情绪处理中起着至关重要的作用，该过程受到神经回路活动的动态调节。然而，目前尚不清楚操纵神经回路活动是否可以达到足够的神经源效应来调节行为。在这里，我们报告，对小鼠下丘脑中乳头上核（SuM）神经元的慢性模式光遗传学刺激可强有力地促进多个阶段的神经发生，从而导致神经干细胞和行为相关的成年神经元（ABN）的产生增加并增强成熟度。从功能上讲，选择性操纵这些 SuM 促进的 ABN 的活性可以调节记忆检索和焦虑样行为。此外，我们发现 SuM 神经元对环境新颖性 (EN) 高度敏感，并且是 EN 诱导的神经发生增强所必需的。此外，在新环境下，SuM 是 ABN 活动依赖性行为调节所必需的。我们的研究确定了一个关键的下丘脑回路，该回路将新奇信号与 ABN 的产生和成熟结合起来，并强调了回路修饰的 ABN 在行为调节中的活动依赖性贡献。