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

<jats:p>Action potentials in mesostriatal dopamine (DA) neurons encode the motivational value of salient stimuli. DA neurons possess extensively branched axonal arbours, and how action potentials are converted to DA output will be influenced dynamically and critically by axonal mechanisms that are poorly understood. We explored the role for mechanisms governing release probability and axonal excitability in determining short-term plasticity (STP) of DA release, using fast-scan cyclic voltammetry in ex vivo mouse striatum. The brief short-term facilitation (STF) and longer short-term depression (STD) seen were only weakly dependent on initial release. Rather, STP was strongly governed by release-independent mechanisms that involved K+-dependent axonal excitability and surprisingly, the dopamine transporter (DAT), particularly in dorsal striatum. The DAT acts as a master regulator of DA STP, governing the balance between release-dependent and release-independent mechanisms that also show region-specific gating.</jats:p>