Dopamine release in the ventral pallidum regulates reward processing — The Association Specialists
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Dopamine release in the ventral pallidum regulates reward processing (21453)

Matthew Williams-Spooner 1 , Lauren Glozier 1 , Kevin Chang 1 , Asheeta Prasad 1
  1. Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia

The ventral pallidum (VP) is a key node for reward processing. However, the functional contribution of dopamine release in the VP is unknown.

Using a discriminative instrumental conditioning paradigm, male rats were first trained to press an active lever to obtain sucrose pellets. This was followed by extinction, reacquisition, and a progressive ratio test to assess motivation. We first performed circuit tracing to identify connections between the VP and midbrain dopamine neurons. We then mapped calcium activity (jGCaMP8m, n=8) and dopamine release (GRABDA, n= 10) in the VP using fibre photometry. Lastly, we used chemogenetics and pharmacologically antagonised dopamine activity to causally demonstrate that VP activity and dopamine release in the VP support reward learning.

Circuit tracing confirmed that the VP receives input from midbrain dopamine. Fibre photometry found that the VP is involved in reward learning, and that reward learning involves dopamine release into the VP.

Using an inhibitory DREADD (Syn-hM4Di-mCherry, n=6) and control (Syn-mCherry, n=6), we then confirmed that inactivating the VP impairs reward learning and reacquisition. Finally, using fluphenazine, an antagonist of D1- and D2-like receptors, we showed that reward-related learning requires dopamine release into the VP.

Thus, using circuit tracing, fibre photometry, chemogenetics, and behavioural pharmacology, we provide converging lines of evidence that the VP is essential for reward learning in rats, and reveal a novel dopamine pathway in reward processing. We also demonstrate how VP activity and dopamine release into the VP map onto reward-related behaviours, such as working to obtain rewards vs consuming rewards.