Characterization of ventromedial hypothalamus activity during exposure to innate and conditioned threats

Abstract

In the face of imminent predatory danger, animals quickly detect the threat and mobilize key survival defensive actions, such as escape and freezing. The dorsomedial portion of the ventromedial hypothalamus (VMH) is a central node in innate and conditioned predator-induced defensive behaviours. Prior studies have shown that activity of steroidogenic factor 1 (sf1)-expressing VMH cells is necessary for such defensive behaviours. However, sf1-VMH neural activity during exposure to predatory threats has not been well characterized. Here, we use single-cell recordings of calcium transients from VMH cells in male and female mice. We show this region is activated by threat proximity and that it encodes future occurrence of escape but not freezing. Our data also show that VMH cells encoded proximity of an innate predatory threat but not a fear-conditioned shock grid. Furthermore, chemogenetic activation of the VMH increases avoidance of innate threats, such as open spaces and a live predator. This manipulation also increased freezing towards the predator, without altering defensive behaviours induced by a shock grid. Lastly, we show that optogenetic VMH activation recruited a broad swath of regions, suggestive of widespread changes in neural defensive state. Taken together, these data reveal the neural dynamics of the VMH during predator exposure and further highlight its role as a critical component of the hypothalamic predator defense system.

Bed nucleus of the stria terminalis GABA neurons are necessary for changes in foraging behaviour following an innate threat

“…Indeed, rat aggression towards mice is observed as predatory behaviour (Horovitz et al, 1966; Ilchibaeva et al, 2017; Tulogdi et al, 2015). In addition, close proximity to a rat elicits a flight response in mice (Deng et al, 2016; Esteban Masferrer et al, 2020; Reis, Lee, et al, 2021; Reis, Liu, et al, 2021; Tobias et al, 2023; Wang, Schuette, La‐Vu, et al, 2021; Wang, Schuette, Nagai, et al, 2021). Thus, this innate threat experience required BNST GABA neurons for the consequential behavioural response in post‐encounter foraging when the predator was no longer present.…”

Hypothalamic representation of the imminence of predator threat detected by the vomeronasal organ in mice

“…These findings suggest that induction of robust freezing behavior is determined by a distinct set of VMH neurons, and the intensity of freezing behavior is encoded separately, possibly by the intensity or dynamics of the neuronal firing, which cannot be detected by the cFos-IR used in this study. The VMHdm/c region contains several subpopulations of neurons that coordinate various defensive behavioral responses (Engelke et al, 2021;Esteban Masferrer et al, 2020;Kennedy et al, 2020;Silva et al, 2016;Tobias et al, 2023). Previous studies have demonstrated that optogenetic stimulation of VMHdm/c neurons induces freezing/immobility responses, suggesting that these neurons mediate freezing behavior in response to predator cues (Kunwar et al, 2015;Wang et al, 2015).…”