Nucleus Accumbens Local Circuit for Cue-Dependent Aversive Learning

Abstract

Response to threatening environmental stimuli requires holistic detection and encoding of important environmental features that dictate threat. Animals need to recognize the likelihood that an environmental stimulus predicts threat and respond to these salient aversive stimuli appropriately. 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. Here, we uncover a nucleus accumbens core local circuit whereby excitatory plasticity facilitates learning and recall of discrete aversive cues. We demonstrate that nucleus accumbens substance P release and long-term excitatory plasticity on dopamine 2 receptor expressing projection neurons is required for learning about aversion-associated cues. Additionally, we found learning and recall were dependent on different projection-neuron subtypes. Our work demonstrates a critical role for Nucleus Accumbens substance P in cue-dependent aversive learning.

65 years of research on dopamine's role in classical fear conditioning and extinction: A systematic review

“…However, varying the location of striatal subregion manipulationsdetermined the effect of D 1 photoinhibition on different phases of fear conditioning. In the nucleus accumbens core, photoinhibition during acquisition attenuated fear acquisition but not recall, while in the ventral tail of the striatum, it attenuated recall but not fear acquisition (Table S8; Belilos et al, 2023; Kintscher et al, 2023). In rats, direct infusion of a D 1 ‐like receptor antagonist into the nucleus accumbens shell before recall increased fear recall, but no effect was observed when infused into other parts of the nucleus accumbens.…”

“…However, photoinhibition of D 2 ‐expressing nucleus accumbens core neurons reduced fear expression during recall but enhanced fear expression during non‐CS+ periods (i.e. between stimulus presentations) when inhibition was targeted to the ventral tail of the striatum (Table S8; Belilos et al, 2023; Kintscher et al, 2023). In rats, infusion of a D 2 ‐like antagonist or agonist into the nucleus accumbens shell prior to recall had no effect on fear recall (Table 7; Albrechet‐Souza et al, 2013).…”

Dynamic representation of appetitive and aversive stimuli in nucleus accumbens shell D1- and D2-medium spiny neurons

“…Despite D1- and D2-MSNs presenting remarkable similarities in activity during conditioning, their response was very distinct in extinction conditions. Sparse evidence suggests that the NAc is important for reward extinction 32,53,54 , and pharmacological blockade of dopamine receptors in the NAc impairs fear extinction learning 55 . Extinction is a fundamental form of inhibitory learning that is important for adapting to changing contingencies within the environment.…”

Electric barrier-induced voluntary abstinence reduces alcohol seeking in male, but not female, iP rats.

“…The NAcC has been implicated in cue-induced alcohol seeking (Chaudhri et al, 2010) and the influence of alcohol-predictive cues on reward seeking behaviors (Corbit et al, 2016). Further, the NAcC facilitates learning and recall of discrete aversive cues (Belilos et al, 2023). Thus, the connectivity patterns observed following voluntary abstinence suggest that learning during electric barrier self-administration could have potentially facilitated the protective effect seen.…”