Serotonin and dopamine are major neuromodulators that are essential for flexible behavior. Both serotonin and dopamine are released from relatively small populations of neurons clustered in the midbrain and brainstem. A unique feature of these neurons is that they receive and integrate diverse inputs from many brain areas, and then broadcast their outputs through long axons to many diverse regions of the brain. Despite the importance of these neurotransmitters in various brain functions in normal behaviors and psychiatric disorders, their regulation remains poorly understood. A critical step toward understanding this question is to identify monosynaptic inputs to these neurons. Conventional tracing methods, however, lack the specificity necessary to elucidate monosynaptic inputs to specific neuron types. To circumvent this problem, we have adapted a retrograde transsynaptic tracing method using a modified rabies virus (Wickersham et al., 2007) and identified monosynaptic inputs to midbrain dopamine neurons (Watabe-Uchida et al., 2012).
In this study, we applied this method to identify monosynaptic inputs to serotonin neurons in the dorsal and median raphe (DR and MR, respectively). Furthermore, we compared these data with monosynaptic inputs to dopamine neurons in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) which we reported previously (Watabe-Uchida et al., 2012). Our results show that DR and MR serotonin neurons receive inputs from spatially-shifted forebrain areas. Furthermore, our comparison of inputs to serotonin and dopamine neurons revealed a global organization of afferent controls for serotonin and dopamine systems.