Corticonigral projections recruit substantia nigra pars lateralis dopaminergic neurons for auditory threat memories
Published September 25, 2025
Output Details
Preprint July 17, 2025
Published September 25, 2025
Description
Dopaminergic neurons (DANs) in the lateral substantia nigra project to the tail of striatum (TS), which is involved in threat conditioning. Auditory cortex also contributes to threatening behaviors, but whether it directly interacts with midbrain DANs and how these interactions might influence threat conditioning remain unclear. Here, functional mapping revealed robust excitatory input from auditory and temporal association cortexes to substantia nigra pars lateralis (SNL) DANs, but not to pars compacta (SNc) DANs. SNL DANs exhibited unique firing patterns, with irregular pacemaking and higher maximal firing, reflecting different channel complements than SNc DANs. Behaviorally, inhibiting cortex to SNL projections impaired memory retrieval during auditory threat conditioning. Thus, we demonstrate robust corticonigral projections to SNL DANs, contrasting with previous observations of sparse cortical input to substantia nigra DANs. These findings distinguish SNL DANs from other nigral populations, highlighting their role in threatening behaviors and expanding knowledge of cortex to midbrain interactions.
Identifier (DOI)
10.1038/s41467-025-63132-8
