Modeling fast dopamine neurotransmission in the nucleus accumbens during behavior.

Recent advances in electrophysiology and voltammetry permit monitoring of dopamine (DA) neuronal activity in real time in the brain of awake animals. Studies using these approaches demonstrate that behaviorally relevant events elicit characteristic patterns of electrical activity in midbrain DA neurons as well as large, transient changes in extracellular DA in the nucleus accumbens (NAc). In addition to providing insight into the role of the DA system in the processing of motor, motivational, and sensory information, the new findings also shed light on fast DA neurotransmission in a behavioral context. This report, (1). summarizes the information obtained by electrophysiological and real-time voltammetric approaches and (2). describes a general model of phasic DA signaling in the NAc that links the observed changes in DA electrical activity and extracellular dynamics. The analysis demonstrates that the behaviorally evoked DA transients are governed by similar mechanisms as those produced by short trains of electrical stimulation. Thus, action potential-dependent release and presynaptic uptake are primary determinants of functional DA levels in the brain during behavior. Interestingly, the model predicts that the same burst of electrical activity generated at DA cell bodies produces markedly different DA dynamics in forebrain projection fields. The distinct changes result from heterogeneous release and uptake rates and may underlie region-specific effects of DA. Auto- and heteroreceptors, as well as other sites of presynaptic control, could further modulate the DA transients.