Mapping Ventral Striatopallidal Circuitry and Synaptic Plasticity in Appetitive Behaviour

The ventral striatopallidal system, comprising nucleus accumbens shell (AcbSh) and ventral pallidum (VP), is a key player in appetitive behaviour. Input from medial prefrontal cortex (mPFC) and projections to lateral hypothalamus (LH) contribute to its roles in drug-seeking and relapse. Although the broad connectivity between the four structures is well-established, much cellular and synaptic detail is lacking. The precise circuitry organisation and possible behaviour-evoked neuroadaptations in cortico-accumbal synapses are poorly understood. This thesis addressed these gaps. Opsin-assisted circuit-mapping demonstrated three disynaptic pathways through the ventral striatopallidal network: AcbSh → VP → LH, mPFC → AcbSh → LH, mPFC → AcbSh → VP. AcbSh innervation of LH-projecting VP neurons was primarily from D1-expressing neurons. Dual retrograde tracing identified VP-projecting and LH-projecting AcbSh neurons as separate subpopulations. Electrophysiology recordings taken at two behavioural timepoints showed distinct presynaptic plasticity at cortico-accumbal synapses of distinct AcbSh subpopulations. Presynaptic depression of mPFC input to VP-projecting AcbSh neurons was observed in animals who self-administered alcoholic beer; this may facilitate downstream VP pathways that promote appetitive seeking. Notably, the magnitude of presynaptic depression predicted alcohol-seeking during reacquisition, demonstrating a mechanistic link between circuit-specific plasticity and relapse propensity. Presynaptic potentiation of mPFC input to LH-projecting AcbSh neurons was detected in animals that experienced social isolation and longer duration of dietary restriction, regardless of self-administration history; it suggests sensitivity to stress in the mPFC → AcbSh → LH circuit branch. This thesis advances our understanding of the organisation of ventral striatopallidal circuits and the synaptic changes associated with appetitive behaviour and relapse, providing novel insights that may inform targeted therapeutic strategies for treating maladaptive reward behaviours.