Cellular physiology of the DRN: Implications for anxiety and depression

In combination, anxiety and depression afflict nearly one-third of the United States adult population. Mood and anxiety disorders have long been linked to dysregulation of the serotonin (5-HT) system. As one of the main sources of 5-HT to the forebrain, the dorsal raphe nucleus (DRN) plays a major role in both of these illnesses. The purpose of this chapter is to describe how in vitro and in vivo electrophysiological properties of DRN 5-HT cells, in relationship to their local and broad anatomical connectivity, relate to the pathophysiology of anxiety and depression. Specific DRN subregions will be discussed with regard to their afferent and efferent connections and how differences in regional discharge properties may contribute to these disorders. Lastly, the impact of two neuromodulators, GABA and nitric oxide, on 5-HT neurotransmission within the DRN and the putative contributions of these transmitters to the stress response will be addressed with the goal of providing insight into alternative treatments for stress-related psychopathology.