Plasticity in striatal dopamine release is governed by release-independent depression and the dopamine transporter

Mesostriatal dopaminergic neurons possess extensively branched axonal arbours. Whether action potentials are converted to dopamine output in the striatum will be influenced dynamically and critically by axonal properties and mechanisms that are poorly understood. Here, we address the roles for mechanisms governing release probability and axonal activity in determining short-term plasticity of dopamine release, using fast-scan cyclic voltammetry in the ex vivo mouse striatum. We show that brief short-term facilitation and longer short term depression are only weakly dependent on the level of initial release, i.e. are release insensitive. Rather, short-term plasticity is strongly determined by mechanisms which govern axonal activation, including K+-gated excitability and the dopamine transporter, particularly in the dorsal striatum. We identify the dopamine transporter as a master regulator of dopamine short-term plasticity, governing the balance between release-dependent and independent mechanisms that also show region-specific gating.