Prodynorphin-expressing neurons in the ventromedial hypothalamus respond to the predatory odor and modulate defensive behaviors

Abstract

The ventromedial hypothalamus (VMH) regulates stress responses and defensive behaviors. However, the neural mechanisms underlying its involvement in threat perception remain incompletely understood. Under exposure to the predatory odor, we found that mice showed decreased investigative behaviors and increased latency to contact with the box with odors. Using single-unit recordings, we observed that the VMH neurons were active during the investigative behavior under exposure to the predatory odor. Notably, prodynorphin (PDYN)-expressing neurons, enriched with neuropeptides within the VMH, were activated by the investigative behavior under exposure to the predatory odor, independent of locomotor activity. Furthermore, optogenetic activation of these PDYN-expressing neurons induced escape-like behaviors and place aversion in male mice, highlighting their functional involvement in threat processing. These findings indicate that PDYN-expressing neurons in the VMH are specifically tuned to detect threat stimuli and play a role in modulating defensive behaviors.

Keywords: Escape behaviors; Investigative behaviors; Prodynorphin; The predatory odor; Threat perception; Ventromedial hypothalamus; in vivo recordings.