Abstract
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.
Highlights
Mesostriatal dopaminergic neurons possess extensively branched axonal arbours
We assessed short-term plasticity of electrically evoked DA release in acute coronal striatal slices for pulses paired at inter-pulse intervals (IPI) of 10–200 ms in dorsolateral striatum and nucleus accumbens core (NAc)
The ratio of DA release evoked by the second pulse compared to a single pulse decreased with IPI in CPu (Fig. 1a, c) and in NAc (Fig. 1b, c)
Summary
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. 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. Short-term plasticity is strongly determined by mechanisms which govern axonal activation, including K+‐gated excitability and the dopamine transporter, in the dorsal striatum. We examine the potential roles for: firstly, initial release; secondly, K+-dependent mechanisms that will govern axonal excitability and repolarization; and thirdly, the dopamine transporter (DAT). DATs have the potential to govern short-term plasticity of DA release via regulation of axonal activation and/or release probability (Pr). We propose a region-specific hierarchy of interacting drivers of short-term plasticity, overseen by DATs, with DATs promoting release-insensitive over releasedependent mechanisms
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