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

Mesostriatal DA neurons possess extensively branched axonal arbours. Whether action potentials are converted to DA output in striatum will be influenced dynamically and critically by axonal properties and mechanisms that are poorly understood. We addressed the roles for mechanisms governing release probability and axonal activity in determining short-term plasticity of DA release, using fast-scan cyclic voltammetry in ex vivo mouse striatum. Brief short-term facilitation (STF) and longer short-term depression (STD) were only weakly dependent on the level of initial release, i.e. were release-insensitive. Rather, short-term plasticity was strongly determined by mechanisms which governed axonal activation, including K+-gated excitability and the dopamine transporter (DAT), particularly in dorsal striatum. We identify the DAT as a master regulator of DA short-term plasticity, governing the balance between release-dependent and independent mechanisms that also show region-specific gating.\n\nKey FindingsO_LIShort-term plasticity in dopamine release is only weakly governed by initial release\nC_LIO_LIShort-term depression is strongly dependent on axonal excitability and activation\nC_LIO_LIThe dopamine transporter controls short-term plasticity and drives short-term depression\nC_LIO_LIDopamine transporters govern the balance between release-dependent and -independent mechanisms\nC_LI