Heterogeneous habenular neuronal ensembles during selection of defensive behaviors

Abstract

Optimal selection of threat-driven defensive behaviors is paramount to an animals survival. The lateral habenula (LHb) is a key neuronal hub coordinating behavioral responses to aversive stimuli. Yet, how individual LHb neurons represent defensive behaviors in response to threats remains unknown. Here we show that, in mice, a visual threat promotes distinct defensive behaviors, namely runaway (escape) and action-locking (immobile-like). Fiber photometry of bulk LHb neuronal activity in behaving animals revealed an increase and decrease of calcium signal time-locked with runaway and action-locking, respectively. Imaging single-cell calcium dynamics across distinct threat-driven behaviors identified independently active LHb neuronal clusters. These clusters participate during specific time epochs of defensive behaviors. Decoding analysis of this neuronal activity unveiled that some LHb clusters either predict the upcoming selection of the defensive action or represent the selected action. Thus, heterogeneous neuronal clusters in LHb predict or reflect the selection of distinct threat-driven defensive behaviors.