Deciphering molecular inputs to CRH neurons from POMC neurons

Classical neurophysiological studies have provided great insights into the adaptive role of stress hormones in energy homeostasis and survival-related behaviors in responses to external and internal threats. More recent viral tracing studies revealed that physically restrained activated mouse corticotropin-releasing hormone neurons (CRHNs) in the paraventricular nucleus (PVN) of the hypothalamus have direct synaptic input from proopiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus (ARC), which is known to be associated with satiety. <b>However</b>, the regularity mechanism underlying these complex neural connections remains to be fully elucidated.<b>In this study</b>, we have leveraged a bioinformatic approach to understand cell-cell communication by analyzing publicly available single-cell RNA sequencing (scRNA-seq) datasets and uncovered a dominance of glutamatergic signaling in POMC-CRHNs interactions. This was further confirmed by viral tracing experiments, indicating that restraint-activated POMC neurons primarily employ glutamatergic marker expression. Our study provides and comprehensive understanding of molecular mechanisms underpinning glutamatergic signaling in POMC-CRHNsin stress-responsive networks.<br>

经典神经生理学研究已为阐明应激激素在能量稳态及应对内外威胁时的生存相关行为中的适应性作用提供了重要见解。近期的病毒示踪研究进一步揭示，物理束缚激活的小鼠下丘脑室旁核（paraventricular nucleus, PVN）内的促肾上腺皮质激素释放激素神经元（corticotropin-releasing hormone neurons, CRHNs），可接收来自下丘脑弓状核（hypothalamic arcuate nucleus, ARC）内阿黑皮素原神经元（proopiomelanocortin neurons, POMC）的直接突触输入，而该核团已知与饱感调控相关。然而，这些复杂神经联结背后的规律性机制仍有待全面阐明。本研究借助生物信息学方法，通过分析公开可用的单细胞RNA测序（single-cell RNA sequencing, scRNA-seq）数据集解析细胞间通信，并揭示了POMC-CRHNs相互作用中谷氨酸能信号传导占据主导地位。该结果后续通过病毒示踪实验得到进一步验证，表明束缚激活的POMC神经元主要表达谷氨酸能标志物。本研究为应激响应网络中POMC-CRHNs的谷氨酸能信号传导相关分子机制提供了全面的认知与解析。