Distinct forms of dopamine transmission control locomotion and learning

Abstract

The neuromodulator dopamine is essential for voluntary movement and learning from experience. While these behaviors often occur simultaneously and rely on overlapping nigrostriatal dopamine circuits, they are also separable and can manifest independently. How a single neuromodulatory system controls such disparate aspects of behavior in parallel remains poorly understood. Here we show that striatal dopamine is released through two spatially and functionally distinct modes that are independently regulated and serve distinct behavioral roles. Eliminating dopamine release underlying bulk extracellular accumulation reveals a spatially restricted mode of transmission that maintains phasic dopamine receptor activation on striatal projection neurons. We find that selective loss of diffuse dopamine impairs striatal circuit excitability and reduces locomotion, while point-to-point transmission is sufficient to maintain striatal spine density and support motor and associative learning. We propose that the geometry of dopamine release determines its behavioral output, a principle that explains the breadth of dopamine’s functions and more broadly elucidates how neurons multiplex different forms of information.