Dopamine prediction error signaling in a unique nigrostriatal circuit is critical for associative fear learning.

Learning by experience that certain cues in the environment predict danger is crucial for survival. How dopamine (DA) circuits drive this form of associative learning is not fully understood. Here, in male mice, we demonstrate that DA neurons projecting to a unique subregion of the dorsal striatum, the posterior tail of the striatum (TS), encode a prediction error (PE) signal during associative fear learning. These DA neurons are necessary specifically during acquisition of fear learning, but not once the fear memory is formed, and are not required for forming cue-reward associations. Notably, temporally-precise inhibition or excitation of DA terminals in TS impairs or enhances fear learning, respectively. Furthermore, neuronal activity in TS is crucial for the acquisition of associative fear learning and learning-induced activity patterns in TS critically depend on DA input. Together, our results reveal that DA PE signaling in a non-canonical nigrostriatal circuit is important for driving associative fear learning.