The synaptic vesicle priming protein Munc13 mediates evoked somatodendritic dopamine release

Abstract

Midbrain dopamine neurons secrete dopamine from their somata and dendrites in addition to their axonal release. Shared and distinct properties have been proposed for somatodendritic and axonal release, but the mechanisms of somatodendritic release remain unclear. We here used mouse genetics, electrophysiology, and imaging to define roles of the synaptic vesicle priming protein Munc13 in somatodendritic release in comparison to axonal secretion. Munc13 ablation in dopamine neurons decreased evoked but not spontaneous somatodendritic dopamine transmission measured as D2 receptor-mediated currents. Imaging with a fluorescent dopamine sensor confirmed this finding and established comparable importance for Munc13 in somatodendritic and axonal secretion. Pharmacological experiments revealed that release from adrenergic terminals contributes to D2 receptor-mediated currents, and their relative contribution was enhanced after Munc13 knockout. Altogether, these data establish important roles for Munc13 in evoked somatodendritic release. These roles are similar to Munc13 functions in axonal dopamine release and at fast synapses. Spontaneous midbrain dopamine release does not necessitate Munc13 in dopamine neurons and may rely on a release pathway that is independent of the prototypical release machinery employed at synapses.