Abstract
Dynamic signaling of mesolimbic dopamine (DA) neurons has been implicated in reward learning, drug abuse, and motivation. However, this system is complex because firing patterns of these neurons are heterogeneous; subpopulations receive distinct synaptic inputs, and project to anatomically and functionally distinct downstream targets, including the nucleus accumbens (NAc) shell and core. The functional roles of these cell populations and their real-time signaling properties in freely moving animals are unknown. Resolving the real-time DA signal requires simultaneous knowledge of the synchronized activity of DA cell subpopulations and assessment of the down-stream functional effect ofDArelease. Because this is not yet possible solely by experimentation in vivo,we combine computational modeling and fast-scan cyclic voltammetry data to reconstruct the functionally relevantDAsignal inDAneuron subpopulations projecting to the NAc core and shell in freely moving rats. The approach provides a novel perspective on real-time DA neuron firing and concurrent activation of presynaptic autoreceptors and postsynaptic targets.Wefirst show that individual differences inDArelease arise from differences in autoreceptor feedback. The model predicts that extracellular DA concentrations in NAc core result from constant baselineDAfiring, whereasDAconcentrations in NAc shell reflect highly dynamic firing patters, including synchronized burst firing and pauses. Our models also predict that this anatomical difference in DA signaling is exaggerated by intravenous infusion of cocaine.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Journal of Neuroscience |
| Vol/bind | 36 |
| Udgave nummer | 1 |
| Sider (fra-til) | 98-112 |
| Antal sider | 15 |
| ISSN | 0270-6474 |
| DOI | |
| Status | Udgivet - 2016 |
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