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. However, the regularity mechanism underlying these complex neural connections remains to be fully elucidated.
In this study, 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-CRHNs in stress-responsive networks.