Dopamine (DA) neurons in the ventral tegmentum and in the substantia nigra are the main source of DA in the basal ganglia and the cortex. These signals are instrumental to motivated behavior, learning, and movement. DA neurons fire in two modes: (1) tonic firing mode at low frequencies that has been argued to control tonic DA levels in the brain and (2) bursting mode, with high frequency spiking packets. The latter is linked with phasic dopamine release signaling reward predictions. While much work has been done on the mechanisms that lead to the two firing modes and how DA neurons go from one to another, these are far from being fully understood. In order to understand these issues, we take a mathematical modelling approach. We developed a circuit model of the ventral tegmental area (VTA) reflecting activity of the DA and GABA neuronal populations, as well as their afferents. We show how the combination of intrinsic cellular excitability together with the structure of the GABAergic synaptic transmission and the glutamatergic inputs allows to control DA cell firing modes. Notably, I will argue that asynchronous inhibition, balanced with asynchronous excitation ensures tonic DA cells firing. Synchronous inhibition leads to burst firing, with intra‑burst frequencies far beyond those supported by simple excitation of DA neurons. Time permitting, I will show how drugs of addiction may modify the firing properties of DA neurons.
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