The Determinants of Specific Pavlovian-Instrumental Transfer in the Nucleus Accumbens Shell

In the service of their basic needs and desires, animals and humans can use information from their environment to guide their choice between actions. In the laboratory, the ability for reward-predictive cues to control action selection is studied through outcome-specific Pavlovian-instrumental transfer (PIT-S), in which a stimulus associated with a particular outcomes biases choice between actions towards the response that earned that same outcome. This thesis investigates the determinants of PIT-S within the nucleus accumbens shell (NAc-S), which is selectively recruited to mediate PIT-S, and is not involved in encoding Pavlovian or instrumental associations. Previous work indicated that delta-opioid receptor (DOR) accumulation at the membrane of cholinergic interneurons (CIN-m) in the NAc-S is triggered during Pavlovian learning, and is positively correlated with PIT-S performance. We took three approaches to investigating the role of DOR accumulation: behavioural and pharmacological manipulation of established receptor accumulation, and chemogenetic manipulation of CINs and the afferents that likely utilize DOR accumulation within the NAc-S to mediate PIT-S. Manipulations of the predictive status of Pavlovian cues that abolished PIT-S failed to reverse established DOR accumulation, suggesting that a region that encodes this information controls the use of DOR accumulation to drive PIT-S. Specific pharmacological internalisation of DOR transiently reduced receptor expression on CIN-m in the NAc-S, indicating that CINs have `memory' for DOR accumulation. PIT-S performance was impaired during the period of DOR reduction, indicating that DOR accumulation on NAc-S CIN-m is necessary, but not sufficient, for PIT-S expression. Inactivation of CINs and BLA terminals within the NAc-S impaired and attenuated PIT-S, respectively. Both contralateral and ipsilateral BLA terminal disconnection from CINs in the NAc-S impaired PIT-S performance, despite ipsilateral BLA-NAc-S disconnection failing to affect PIT-S in previous studies, which complicates our ability to interpret this finding. These findings, considered together, suggest that DOR accumulation on CIN-m is necessary, but not sufficient, for PIT-S, and that a functional circuit between BLA terminals and CINs mediates PIT-S, via DOR accumulation on CIN-m