Differential projections of dorsal raphe nucleus neurons to the lateral septum and striatum

The dorsal raphe nucleus (DRN)–serotonin (5-HT) system has been implicated in acute responses to stress and stress-related psychiatric disorders such as anxiety and depression. Stress alters serotonin (5-HT) release in a regionally specific manner. For example, swim stress increases extracellular levels of 5-HT in the striatum and decreases levels in the lateral septum. This finding suggests that the 5-HT efferents to the striatum and lateral septum arise from distinct populations of DRN neurons that are differentially affected by swim stress. To further examine this, retrograde axonal transport of fluorescent RetroBeads™ was used to identify the distribution of DRN neurons projecting to the lateral septum and striatum in the rat brain. Retrograde labeling from the lateral septum was observed primarily within the more caudal portions of the DRN, while labeling from the striatum was observed in neurons located in the more rostral regions of the DRN. Few cell bodies were observed that were labeled from both the striatum and lateral septum suggesting that DRN neurons do not send collateralized projections to the septal region and striatum. Many septal- and striatal-projecting neurons in the DRN exhibited 5-HT, and collateralized projections, when observed, were immunoreactive for 5-HT. Taken together with previous microdialysis studies, these results support the existence of distinct DRN–5-HT-forebrain projections that are differentially regulated by stress.