Retrograde tracing of projections between the nucleus submedius, the ventrolateral orbital cortex, and the midbrain in the rat.

The fluorescent tracers fluoro-gold and 1,1'-dioctadecyl-3,3,3,3-tetramethyl indocarbocyanine perchlorate were used as retrograde markers to examine reciprocal connections between the rat nucleus submedius and the ventrolateral orbital cortex. In addition, midbrain projections to each of these regions were examined. In the prefrontal cortex, we found that input from the nucleus submedius terminates rostrally within the lateral and ventral areas of the ventrolateral orbital cortex. Conversely, the cortical input to the nucleus submedius originates from the medial and dorsal parts of the ventrolateral orbital cortex. Our data also demonstrated that neurons from the ventrolateral periaqueductal gray and the raphe nuclei project to the midline nuclei of the thalamus, including a small projection to the nucleus submedius. We further determined that regions within the ventrolateral periaqueductal gray and raphe nuclei project to the ventrolateral orbital cortex, and that these regions overlap with those that project to the nucleus submedius. These findings suggest that the nucleus submedius might be part of a neural circuit involved in the activation of endogenous analgesia.