Optogenetic Stimulation of Midbrain Dopamine Neurons Produces Striatal Serotonin Release

Abstract

Targeting neurons with light-driven opsins is widely used to investigate cell-specific responses. We transfected midbrain dopamine neurons with the excitatory opsin Chrimson. Extracellular basal and stimulated neurotransmitter levels in the dorsal striatum were measured by microdialysis in awake mice. Optical activation of dopamine cell bodies evoked terminal dopamine release in the striatum. Multiplexed analysis of dialysate samples revealed that the evoked dopamine was accompanied by temporally coupled increases in striatal 3-methoxytyramine, an extracellular dopamine metabolite, and in serotonin. We investigated a mechanism for dopamine−serotonin interactions involving striatal dopamine receptors. However, the evoked serotonin associated with optical stimulation of dopamine neurons was not abolished by striatal D1-or D2-like receptor inhibition. Although the mechanisms underlying the coupling of striatal dopamine and serotonin remain unclear, these findings 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.

Molecular Design of SERTlight: A Fluorescent Serotonin Probe for Neuronal Labeling in the Brain

“…5HT acts as a modulatory neurotransmitter, exerting its effects through activation of a broad palette of 5HT receptors (5HTRs), all of which, with the exception of 5HT3R, are G protein-coupled receptors (GPCRs). 5HT modulates excitatory and inhibitory cells including direct modulation of excitatory and inhibitory synapses via triad synaptic connections. , Further, 5HT has a complex mutual modulatory relationship with the other modulatory neurotransmitters, such as dopamine and endocannabinoids. − …”