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[Preprint]. 2023 Oct 9:2023.02.06.527338. Originally published 2023 Feb 7. [Version 2] doi: 10.1101/2023.02.06.527338

Nucleus Accumbens Local Circuit for Cue-Dependent Aversive Learning

Andrew Belilos, Cortez Gray, Christie Sanders, Destiny Black, Elizabeth Mays, Christopher T Richie, Ayesha Sengupta, Holly S Hake, T Chase Francis
PMCID: PMC9934565  PMID: 36798245

Abstract

Response to threatening environmental stimuli requires detection and encoding of important environmental features that dictate threat. Aversive events are highly salient which promotes associative learning about stimuli that signal this threat. The nucleus accumbens is uniquely positioned to process this salient, aversive information and promote motivated output, through plasticity on the major projection neurons in the brain area. We uncovered a nucleus accumbens core local circuit whereby excitatory plasticity facilitates learning and recall of discrete aversive cues. We demonstrate that putative nucleus accumbens substance P release and long-term excitatory plasticity on dopamine 2 receptor expressing projection neurons is required for cue-dependent fear learning. Additionally, we found fear learning and recall were dependent on distinct projection-neuron subtypes. Our work demonstrates a critical role for Nucleus Accumbens substance P in cue-dependent aversive learning.

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