Collateralized dorsal raphe nucleus projections: A mechanism for the integration of diverse functions during stress

The midbrain dorsal raphe nucleus (DR) is the origin of the central serotonin (5-HT) system, a key neurotransmitter system that has been implicated in the expression of normal behaviors and in diverse psychiatric disorders, particularly affective disorders such as depression and anxiety. One link between the DR-5-HT system and affective disorders is exposure to stressors. Stress is a major risk factor for affective disorders, and stressors alter activity of DR neurons in an anatomically specific manner. Stress-induced changes in DR neuronal activity are transmitted to targets of the DR via ascending serotonergic projections, many of which collateralize to innervate multiple brain regions. Indeed, the collateralization of DR efferents allows for the coordination of diverse components of the stress response. This review will summarize our current understanding of the organization of the ascending DR system and its collateral projections. Using the neuropeptide corticotropin-releasing factor (CRF) system as an example of a stress-related initiator of DR activity, we will discuss how topographic specificity of afferent regulation of ascending DR circuits serves to coordinate activity in functionally diverse target regions under appropriate conditions.