A striatal circuit balances learned fear in the presence and absence of sensory cues

Summary

During fear learning, defensive behaviors need to be finely balanced, to allow animals to return to normal behaviors after the termination of threat-indicating sensory cues. Nevertheless, the circuits underlying such balancing are largely unknown. Here, we investigate the role of direct (D1R+) - and indirect (Adora+) pathway neurons of the amygdala-striatal transition zone (AStria) in fear learning. In-vivo Ca²⁺ imaging revealed that fear learning increased the responses of D1R+ AStria neurons to an auditory CS, given that the animal moved. In Adora+ neurons, fear learning also induced a differential activity during freezing and movement, albeit with little influence of the CS. In-vivo optogenetic silencing during the training day showed that plasticity in D1R+ AStria neurons contributes to auditory-cued fear memories, whereas Adora+ neurons suppressed learned freezing when no CS was present. Circuit tracing experiments identified cortical input structures to the AStria, and recording of optogenetically-evoked EPSCs at the corresponding projection revealed different forms of long-term plasticity at synapses onto D1R+ and Adora+ AStria neurons. Taken together, direct- and indirect pathways neurons of the AStria show differential signs of in-vivo and ex-vivo plasticity after fear learning, and balance defensive behaviors in the presence and absence of aversively motivated sensory cues.