A Parabrachial to Hypothalamic Pathway Mediates Defensive Behavior

Abstract

AbstractDefensive behaviors are critical for animal’s survival. Both the paraventricular nucleus of the hypothalamus (PVN) and the parabrachial nucleus (PBN) have been shown to be involved in defensive behaviors. However, whether there are direct connections between them to mediate defensive behaviors remains unclear. Here, by retrograde and anterograde tracing, we uncover that cholecystokinin (CCK)-expressing neurons in the lateral PBN (LPBCCK) directly project to the PVN. Byin vivofiber photometry recording, we found that LPBCCKneurons actively respond to various threat stimuli. Selective photoactivation of LPBCCKneurons promotes aversion and defensive behaviors. Conversely, photoinhibition of LPBCCKneurons attenuates rat or looming stimuli-induced flight responses. Optogenetic activation of LPBCCKaxon terminals within the PVN or PVN glutamatergic neurons promote defensive behaviors. Whereas chemogenetic and pharmacological inhibition of local PVN neurons prevent LPBCCK-PVN pathway activation-driven flight responses. These data suggest that LPBCCKneurons recruit downstream PVN neurons to actively engage in flight responses. Our study identifies a previously unrecognized role for the LPBCCK-PVN pathway in controlling defensive behaviors.