A circuit from the ventral subiculum to anterior hypothalamic nucleus GABAergic neurons essential for anxiety-like behavioral avoidance.

Behavioral observations suggest a connection between anxiety and predator defense, but the underlying neural mechanisms remain unclear. Here we examine the role of the anterior hypothalamic nucleus (AHN), a node in the predator defense network, in anxiety-like behaviors. By in vivo recordings in male mice, we find that activity of AHN GABAergic (AHN Vgat+ ) neurons shows individually stable increases when animals approach unfamiliar objects in an open field (OF) or when they explore the open-arm of an elevated plus-maze (EPM). Moreover, object-evoked AHN activity overlap with predator cue responses and correlate with the object and open-arm avoidance. Crucially, exploration-triggered optogenetic inhibition of AHN Vgat+ neurons reduces object and open-arm avoidance. Furthermore, retrograde viral tracing identifies the ventral subiculum (vSub) of the hippocampal formation as a significant input to AHN Vgat+ neurons in driving avoidance behaviors in anxiogenic situations. Thus, convergent activation of AHN Vgat+ neurons serves as a shared mechanism between anxiety and predator defense to promote behavioral avoidance.