TY - JOUR T1 - Neuron-type specificity of dorsal raphe projections to ventral tegmental area JF - bioRxiv DO - 10.1101/2021.01.06.425641 SP - 2021.01.06.425641 AU - Anna J. Chang AU - Lihua Wang AU - Federica Lucantonio AU - Maya Adams AU - Andy Lemire AU - Joshua T. Dudman AU - Jeremiah Y. Cohen Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/01/07/2021.01.06.425641.abstract N2 - The midbrain dorsal raphe (DR) and ventral tegmental area (VTA) contain two of the brain’s main ascending neuromodulatory transmitters: serotonin and dopamine. We studied the pathway from DR to VTA using single-cell RNA sequencing, anatomical tracing, and electrophysiology and behavior in mice. Single-cell sequencing confirmed a differential distribution of dopamine cell types between medial and lateral aspects of the VTA. This molecular diversity included differential expression of a subset of glutamatergic and serotonergic receptors. Anatomical data showed that distinct serotonergic and glutamatergic populations of DR neurons project to distinct medial-lateral locations in VTA. Physiological data showed that serotonergic neurons are positioned to excite putative dopaminergic neurons in lateral VTA on short timescales (within trial), and inhibit them on long timescales (on the next trial). Our results reveal precise anatomical specificity of DR projections to VTA, and suggest a functional role for serotonergic modulation of dopaminergic function across multiple timescales.Competing Interest StatementThe authors have declared no competing interest. ER -