Presynaptic Partners of Dorsal Raphe Serotonergic and GABAergic Neurons

The serotonin system powerfully modulates physiology and behavior in health and disease, yet the circuit mechanisms underlying serotonin neuron activity are poorly understood. The major source of forebrain serotonergic innervation is from the dorsal raphe nucleus (DR), which contains both serotonin and GABA neurons. Using viral tracing combined with electrophysiology, we found that GABA and serotonin neurons in the DR receive excitatory, inhibitory, and peptidergic inputs from the same specific brain regions. Embedded in this overall similarity are important differences. Serotonin neurons are more likely to receive synaptic inputs from anterior neocortex while GABA neurons receive disproportionally higher input from the central amygdala. Local input mapping revealed extensive serotonin-serotonin as well as GABA-serotonin connectivity with a distinct spatial organization. Covariance analysis suggests heterogeneity of both serotonin and GABA neurons with respect to the inputs they receive. These analyses provide a foundation for further functional dissection of the serotonin system. •Dorsal raphe serotonin (5HT) and GABA neurons receive biased input from the same regions•Cortical inputs to 5HT and GABA neurons differ in connectivity and synaptic properties•Local input to 5HT neurons is spatially organized and includes many 5HT-5HT connections•Evidence for extensive input heterogeneity, from long-range to local connectivity Serotonin modulates physiology and behavior in health and disease, yet the circuits that control serotonin neuron activity are poorly understood. Here, Weissbourd et al. map presynaptic inputs to dorsal raphe serotonin and GABA neurons, revealing specific local and long-range connectivity.