A Neural Circuit from the Dorsal CA3 to the Dorsomedial Hypothalamus Mediates Transition Between Risk Exploration and Defense

Abstract

An appropriate transition between explorative and defensive behavior is essential for the reproduction and survival of prey animals in risky environments. However, the neural circuit and mechanism that allow for such a switch remains poorly understood. Here, we used a semi-naturalistic predator threat test (PTT) to observe and quantify the defense-exploration transition in mice. During PTT, ~80% of putative dorsal CA3 glutamatergic neurons (dCA3^Glu) responded positively to contextual exploration, but negatively to risky exploration. Their activation induces a significant transition from defensive to exploratory behavior. A disynaptic circuit, comprising the dorsal CA3, dorsal lateral septal, and dorsomedial hypothalamic (dCA3^Glu-dLS^GABA-DMH) areas, may be involved. Approximately 60% of putative dLS^GABA and ~70% of putative DMH^Glu negatively responded to a threat context. Therefore, activation of the dCA3^Glu-dLS^GABA-DMH circuit promotes the transition from defense to exploration and suppresses threat-induced increase in arousal.

Keywords: risk exploration, defensive behavior, dorsal CA3, dorsal lateral septum, dorsomedial hypothalamus, arousal