Sparse Populations of Dopaminergic and Non-dopaminergic Neurons Regulate Downstream Dopamine Release in the Nucleus Accumbens Stephen Cowen , Daniel F. Hill, Zachary Olson, Mitchell J. Bartlett, Torsten Falk, Michael L. Heien, Stephen L. Cowen (Psychology, University of Arizona, Tucson, ARIZONA ) P1
Dopamine release is known for its role in assigning value to rewards, motivation, reinforcement learning, and memory formation. Dysregulation of dopamine signaling is also implicated in pathological conditions such as depression, schizophrenia, Parkinson's disease, and addiction. Dopamine is released from neurons in the midbrain ventral tegmental area (VTA) and acts on dopamine receptors in the nucleus accumbens (NAc) to modulate learning and motivation. Dopaminergic terminals in the NAc are thought to release dopamine in response to large population-level burst activity in the VTA. However, the exact relationship between VTA cell activity and NAc dopamine release has not been established due to technological limitations that have prevented simultaneous measurement of both dopamine release and neural activity. To address this, we collected simultaneous measurements of cell firing in the VTA and dopamine release in the NAc using a novel measurement tool developed in our laboratory that integrates extracellular electrophysiological recording with fast-scan cyclic voltammetry (FSCV). We then measured neural activity in the VTA and spontaneous dopamine release in the NAc in anesthetized rats. We predicted that most VTA dopamine neurons would respond to dopamine release events in the NAc. In contrast, we found that only ~10% of dopamine neurons responded to dopamine release events, and that at greater proportion of putative non-dopaminergic inhibitory neurons were activated before and during each dopamine release event. Taken together, these data suggest that NAc dopamine release is encoded by a surprisingly sparse set of VTA dopamine neurons that are under tight control by a complex network of non-dopaminergic cells.