Distinct channels of the ventral striatopallidal circuitry

The nucleus accumbens shell (AcbSh) and ventral pallidum (VP) comprise the ventral striatopallidal system. Their connections with the lateral hypothalamus (LH) and medial prefrontal cortex (mPFC) are important in appetitively motivated behaviours and conditions like addiction. These regions have different neuronal subtypes and how they are specifically connected between them have been poorly understood. To investigate the circuitry between AcbSh, VP, LH and mPFC, we performed channelrhodopsin-assisted circuit-mapping using whole-cell patch-clamp electrophysiology and retrograde tracing in wild-type, D1-Cre and A2A-Cre Long Evans rats. We found that VP neurons received different inhibitory AcbSh inputs depending on their projection profile: VP neurons that project to LH predominantly receive input from D1-AcbSh whereas VP neurons that do not project there receive mixed D1- and D2-AcbSh input. This indicates a disynaptic D1-AcbSh to VP to LH channel. Furthermore, we found that mPFC projections to AcbSh created two disynaptic channels with different input to these two AcbSh outputs – mPFC synapses onto a higher proportion of VP-projecting neurons than LH-projecting neurons. Combined with past work, these results suggest there are distinct ventral striatopallidal channels that diverge at AcbSh to exert different control over LH: a direct inhibitory path to LH and an indirect disynaptic path via VP that is disinhibitory. Ongoing work is investigating synaptic plasticity in animals that undergo alcohol self-administration to examine the synaptic strength of mPFC input to the two AcbSh channels. A stronger knowledge of the ventral striatopallidal circuitry and its different channels can help understand their roles in appetitively motivated behaviours.