Hippocampal-hypothalamic circuit controls context-dependent innate defensive responses

Abstract

Preys use their memory - where they sensed a predatory threat and whether a safe shelter is nearby - to dynamically control their survival instinct to avoid harm and reach safety. However, it remains unknown which brain regions are involved, and how such top-down control of innate behaviour is implemented at the circuit level. Here, we show that the anterior hypothalamic nucleus (AHN) is best positioned to perform this task as an exclusive target of the hippocampus (HPC) within the medial hypothalamic defense system. Selective optogenetic stimulation and inhibition of hippocampal inputs to the AHN revealed that the HPC→AHN pathway not only mediates the contextual memory of predator threats but also controls the goal-directed escape by transmitting information about the surrounding environment. These results reveal a new mechanism for experience-dependent, top-down control of innate defensive behaviours.

Neural activity and theta rhythmicity in the anterior hypothalamic nucleus are involved in regulating social investigation

“…Several previous studies that directly examined the effect of stimulating or inhibiting AHN neurons have yielded contradicting results. While some of them concluded that AHN stimulation cause escape response (Bang et al, 2022; Wang et al, 2015), others suggested the opposite (Anthony et al, 2014). Yet, none of these studies examined the role of the AHN in a social context.…”

“…The AHN is a relatively understudied and poorly defined brain area, known as part of the medial hypothalamic defensive system (Canteras, 2002). It includes mainly inhibitory GABAergic neurons (Bang et al, 2022; Wang et al, 2015; Xie et al, 2022) which largely project to several brain regions thought to be central to fight-or-flight behavior, such as the lateral septum (LS) and dorsal periaqueductal gray (dPAG) area (Risold et al, 1994; Xie et al, 2022). In rats and mice, the AHN was shown to take part in responses to predators (Cezario et al, 2008; Martinez et al, 2008; Mendes-Gomes et al, 2020) as well as in regulating parental behavior (Tachikawa et al, 2013).…”

“…In rats and mice, the AHN was shown to take part in responses to predators (Cezario et al, 2008; Martinez et al, 2008; Mendes-Gomes et al, 2020) as well as in regulating parental behavior (Tachikawa et al, 2013). In recent years, several studies explored the role of AHN neurons in the context of anxiety and avoidance behaviors, using advanced techniques (e.g., optogenetics), with contradicting results (Anthony et al, 2014; Bang et al, 2022; Wang et al, 2015). Yet, none of these studies examined the role of the AHN in the context of social behavior.…”

Activation of the fear-responsive anterior hypothalamic area promotes avoidance and triggers compulsive grooming behavior in mice

“…A recent study showed that contextual learning influences AHA neuronal activity in part through hippocampal inputs that enhance goal-directed escape behavior 7 . Therefore, we first investigated whether a classic foot shock-cue conditioning paradigm modulates AHA neuronal activity.…”

“…Robust escape behaviors such as increases in locomotor activity and jumping were triggered by the activation of the VMH→AHA pathway 6 . Moreover, activation of hippocampal inputs to the AHA promotes contextual control of such behaviors 7 . Thus, these findings raise questions about the etiological role of AHA neuronal activation in stress-related and compulsive disorders 8 .…”