Optogenetic Stimulation of Midbrain Dopamine Neurons ProducesStriatal Serotonin Release

Targeting neurons with light-driven opsins is widely used toinvestigate cell-specific responses. We transfected midbrain dopamine neuronswith the excitatory opsin Chrimson. Extracellular basal and stimulatedneurotransmitter levels in the dorsal striatum were measured by microdialysisin awake mice. Optical activation of dopamine cell bodies evoked terminaldopamine release in the striatum. Multiplexed analysis of dialysate samplesrevealed that the evoked dopamine was accompanied by temporally coupledincreases in striatal 3-methoxytyramine, an extracellular dopamine metabolite,and in serotonin. We investigated a mechanism for dopamine-serotonininteractions involving striatal dopamine receptors. However, the evokedserotonin associated with optical stimulation of dopamine neurons was notabolished by striatal D1- or D2-like receptor inhibition. Although the mechanismsunderlying the coupling of striatal dopamine and serotonin remain unclear, thesefindings illustrate advantages of multiplexed measurements for uncovering functional interactions between neurotransmitter systems.Furthermore, they suggest that the output of optogenetic manipulations may extend beyond opsin-expressing neuronal populations.

Automated summary

Targeting neurons with light-driven opsins is a commonly used approach to study cell-specific responses. In this study, the activation of dopamine neurons resulted in the release of dopamine and serotonin in the striatum, suggesting a potential interaction between these two neurotransmitters.