Corticonigral projections recruit substantia nigra pars lateralis dopaminergic neurons for auditory threat memories

Abstract Dopaminergic neurons (DANs) in the substantia nigra pars lateralis (SNL) project to the tail of striatum, where they contribute to threat behaviors. Auditory cortex contributes to threat conditioning, but whether it directly modulates DANs is unclear. Here, we show that SNL DANs fire irregularly, achieve rapid maximal firing rates, exhibit distinct ionic conductances, and receive predominantly excitatory input. This contrasts with substantia nigra pars compacta (SNc) DANs that fire regularly and receive mainly inhibitory input, establishing SNL DANs as a physiologically distinct dopaminergic subpopulation. Functional mapping revealed robust excitatory input from auditory and temporal association cortices to SNL DANs, but not SNc DANs. In behavioral experiments, inhibiting neurotransmitter release from either SNL DANs or cortical afferents to SNL resulted in impaired auditory threat conditioning. Thus, our work reveals robust functional corticonigral projections to SNL DANs which directly regulate threat behaviors.