Serotoninergic projections from the dorsal raphe nucleus to the nucleus submedius in the rat and cat

The nucleus submedius in the medial thalamus has been known to receive spinothalamic and trigeminothalamic fibers, and to contain neurons which can be activated by noxious stimuli. These previous findings suggest that the nucleus submedius may be involved in the processing and relay of pain-related information. In the present study, we immunohistochemically observed in the rat and cat that the nucleus submedius was distributed with a considerable amount of serotoninergic fibers. After iontophoretic injection of cholera toxin B subunit into the nucleus submedius, the sequential double-antigen immunofluorescence histochemistry for retrogradely transported cholera toxin B subunit and serotonin revealed that the serotoninergic fibers to the nucleus submedius arose mainly from the dorsal raphe nucleus, and additionally from the ventrolateral and medial parts of the midbrain periaqueductal gray. The direct projections from the dorsal raphe nucleus to the nucleus submedius were confirmed by anterograde axonal tracing after iontophoretic injection of Phaseolus vulgaris-leucoagglutinin into the dorsal raphe nucleus. The disappearance of almost all serotoninergic fibers in the nucleus submedius was also observed after destruction of the dorsal raphe nucleus. The fluorescent retrograde double-labeling with Diamidino Yellow and Fast Blue further revealed that some neurons in the dorsal raphe nucleus projecting directly to the nucleus submedius sent their axon collaterals to the ventrolateral orbital region of the cerebral cortex, nucleus accumbens, amygdala, nucleus raphe magnus, caudal spinal trigeminal nucleus, or spinal cord. The possible roles of the serotoninergic projections from the dorsal raphe nucleus to the nucleus submedius in pain control and/or the olfactolimbic functions are discussed.