State- and circuit-dependent opponent-processing of fear

Read the full article See related articles

Listed in

This article is not in any list yet, why not save it to one of your lists.
Log in to save this article


The presence of valence coding neurons in the basolateral amygdala (BLA) that form distinct projections to other brain regions implies functional opposition between aversion and reward during learning. However, evidence for opponent interactions in fear learning is sparse and may only be apparent under certain conditions. Here we test this possibility by studying the roles of the BLA➔central amygdala (CeA) and BLA➔nucleus accumbens (Acb) pathways in fear learning in male rats. First, we assessed the organisation of these pathways in the rat brain. BLA➔CeA and BLA➔Acb pathways were largely segregated in the BLA but shared overlapping molecular profiles. Then we assessed activity of the BLA➔CeA and BLA➔Acb pathways during two different forms of fear learning - fear learning in a neutral context and fear learning in a reward context. BLA ➔ CeA neurons were robustly recruited by footshock regardless of where fear learning occurred whereas recruitment of BLA➔Acb neurons was state-dependent because footshock only recruited this pathway in a reward context. Finally, we assessed the causal roles of activity in these pathways in fear learning. Photoinhibition of the BLA➔CeA pathway during the footshock US impaired fear learning, regardless of where fear learning occurred. In contrast, photoinhibition of the BLA➔Acb pathway augmented fear learning, but only in the reward context. Taken together, our findings show circuit- and state-dependent opponent processing of fear. Footshock-driven activity in the BLA➔Acb pathway can functionally oppose the BLA➔CeA pathway to limit how much fear is learned.

Significance Statement

Here we identify a fear opponent process in the brain. We show that an aversive event can recruit distinct populations of neurons in the rat basolateral amygdala. One population projects to the central amygdala to promote fear learning. A second population projects to the nucleus accumbens to oppose fear learning. These nucleus accumbens projecting neurons limit how much fear is learned and are candidates for therapeutic targeting to minimize the amount of fear learned after a traumatic experience.

Article activity feed