TOPOGRAPHY OF SEROTONIN NEURONS IN THE DORSAL RAPHE NUCLEUS THAT SENDAXON COLLATERALS TO THE RAT PREFRONTAL CORTEX AND NUCLEUS-ACCUMBENS

Diverse physiological actions have been reported for 5-hydroxytryptami ne (5-HT, serotonin) in the medial prefrontal cortex (MPFC) and the nu cleus accumbens (Acb) suggesting that the 5-HT innervation of these fo rebrain areas may be derived from different populations of neurons. We examined this possibility by mapping the distribution of 5-HT-immunor eactive (ir) and non-5-HT-ir neurons containing retrograde labeling fo llowing injections of different tracers into both these target regions . The analysis was focused in the dorsal raphe nucleus (DRN) of the mi dbrain, since 5-HT pathways to the MPFC and Acb primarily originate fr om this area. Volume microinjections of the fluorescent retrograde tra cer, Fluoro-Gold (FG), were placed into the MPFC and microinjections o f cholera toxin B subunit coupled to 15 nm gold particles (CT-Au) were placed into the Acb of the same animal. Sections through the DRN cont aining retrogradely labeled neurons were further processed for immunof luorescent localization of 5-HT using a rhodamine marker. Neurons retr ogradely labeled from the Acb were greater in number overall than thos e projecting to the MPFC. In addition, Acb-projecting neurons extended into the lateral wings of the DRN, whereas MPFC-projecting neurons we re more restricted to the midline. Both groups of retrogradely labeled neurons, however, were more numerous in the caudal aspect of the dors al raphe nucleus and were scattered amongst 5-HT immunoreactive perika rya. Of 783+/-69 CT-Au labeled cells, 15% also contained the FG label and 11% contained FG and 5-HT immunoreactivity. Of 613+/-48 FG labeled cells, 24% also contained the CT-Au label and 21% were also immunorea ctive to 5-HT. The results suggest a more prominent input to the Acb f rom both 5-HT-ir and non-5-HT-ir neurons in the caudal aspect of the D RN and further indicate that while most 5-HT-ir and non-5-HT-ir neuron s project differentially to both forebrain regions, a few cells also s how collateralization to the MPFC and Acb. Such collateralization of s ingle serotonergic neurons to divergent targets may integrate cognitiv e and motor activities in response to pharmacological manipulations of ascending serotonergic pathways.