Generating bursts (and pauses) in the dopamine midbrain neurons.

Dopamine (DA) midbrain neurons project to several striatal and cortical target areas and are essentially involved in a puzzling variety of important brain functions such as action selection and motor performance, motivation and reward-based learning, but also working memory and cognition. These neurons act via the release of their (main) neurotransmitter, dopamine, which binds to metabotropic dopamine receptors of the D1 or D2 type on target neurons. Axonal but also dendritic dopamine release is essentially controlled by calcium-triggered exocytosis of dopamine-filled synaptic vesicles primarily driven by electrical activity of the dopamine neuron, which generates patterns of actions potentials in the somato-dendritic domain and distributes them along its axonal tree. Thus, recording the behaviorally relevant pattern of electrical activity in DA neurons and identifying the underlying biophysical mechanisms that integrate afferent synaptic inputs and intrinsic excitability constitute a crucial element for defining the physiological roles of the midbrain DA system. Electrical activity of midbrain DA neurons in vivo is characterized by tonic background activity in a narrow frequency range (ca. 1-8Hz) interrupted by either transient (i.e. phasic, <500ms) sequences of high-frequency firing (>15Hz), so called "bursts", or transient pauses of electrical activity, where DA neurons generate no action potentials. This review focuses on the properties of these phasic activity changes in midbrain DA neurons. It updates recent progress on the expanding behavioral contexts, associated with phasic electrical activity in DA neurons beyond the classical (canonical) reward prediction error model. The review also highlights recently defined contributions of synaptic inputs for burst and pause generation and the roles of distinct postsynaptic ion channels in midbrain DA neurons.