Distinct microcircuits in the dorsal raphe to ventral tegmental area projection pathway

Dopamine and gamma-aminobutyric acid (GABA) neurons in the ventral tegmental area have been shown to be critically involved in motivational behavior. How these neurons encode the relevant features of motivational behavior to generate behavioral output is still unclear. To investigate this question, we examined one of the major afferent sources of the ventral tegmental area, the dorsal raphe. We first characterized the anatomical underpinnings of the dorsal raphe to ventral tegmental area projection pathway. We found that this major projection pathway is composed of microcircuits in which distinct topographical and chemical clusters of dorsal raphe neurons project to different parts (medial-lateral axis) of the ventral tegmental area. We next characterized the functional connectivity of one of the described microcircuits, in which dorsolateral dorsal raphe serotonin neurons project to lateral ventral tegmental area. We found that serotonergic axonal stimulation using optogenetics elicited a phasic excitatory response on dopamine neurons, but not on GABA neurons. This stimulation, either unilaterally or bilaterally, did not affect classical conditioning behavior, consistent with our finding that the firing rate of GABA neurons are more tightly correlated with behavioral output than the firing rate of dopamine neurons on a trial-by-trial basis. Together, these results describe distinct anatomical and functional microcircuits in the dorsal raphe to ventral tegmental area projection pathway