Heterogeneous neuronal activity in the ventral tegmental area coordinates dopamine release in the nucleus accumbens

Abstract

Dopamine release in the ventral striatum is fundamental to adaptive appetitive behavior. Frustratingly, technological, and methodological hurdles have limited the investigation of the mechanisms that drive phasic dopamine release. Although dopamine neuron activation in the ventral tegmental area (VTA) surely results in dopamine release, how populations of these neurons coordinate their activities in time to modulate the temporal pattern of release remains unclear. Additionally, burgeoning evidence suggests that control over striatal dopamine release is not solely regulated by the burst firing of VTA neurons or even cell-body activation of these neurons. Here, we recorded VTA neurons while simultaneously monitoring pharmacologically induced phasic dopamine release events in the ventral striatum (nucleus accumbens core) of anesthetized rats. On average, dopaminergic and non-dopaminergic neurons increased activity at the time of the onset of release and decreased at the time of peak release; however, the tuning of individual VTA neurons to dopamine release was notably heterogenous, with subsets of neurons responding prior to release, at release onset, or during release. Other neurons were notably silent during release but active otherwise. Interestingly, both putative dopaminergic and non-dopaminergic neurons expressed this temporally heterogeneous response pattern. Furthermore, the firing activity of dopaminergic, but not non-dopaminergic neurons, correlated with the magnitude of dopamine release. These data suggest that populations of VTA neurons become active at distinct times of a dopamine release event to sculpt the temporal pattern of release.