Calcitonin gene-related peptide immunoreactivity in the visceral sensory cortex, thalamus, and related pathways in the rat.

It has been proposed that calcitonin gene-related peptide (CGRP) may serve as a major neuromodulator in visceral sensory pathways, but its exact role in the visceral sensory thalamus and cortex has not been determined. We therefore examined the distribution of CGRP-like immunoreactive (CGRPir) innervation of the insular cortex and the parvicellular division of the ventroposterior nucleus of the thalamus (VPpc) in the rat by using immunohistochemistry for CGRP combined with retrograde transport of the fluorescent dye fluoro-gold. Modest numbers of CGRPir fibers were distributed in the dysgranular and agranular insular cortex, but few were observed in the granular insular cortex. The density of CGRPir innervation increased caudally along the rhinal fissue and was considerably greater in the perirhinal cortex. When fluoro-gold was injected into the insular cortex numerous retrogradely labeled neurons were seen in the VPpc, but few of these were CGRPir. Retrogradely labeled CGRPir neurons were, however, seen in the ventral lateral and medial parabrachial (PB) subnuclei. Injection of fluoro-gold into the perirhinal cortex (which is just caudal to the insular cortex along the rhinal fissure) resulted in many retrogradely labeled CGRPir neurons in the posterior thalamic region, including the subparafascicular, the lateral subparafascicular, and the posterior intralaminar nuclei. The VPpc was heavily innervated by CGRPir fibers but contained few CGRPir cell bodies. Injection of fluoro-gold into the VPpc resulted in many retrogradely labeled CGRPir neurons in the external medial PB subnucleus bilaterally, but with a contralateral predominance. Smaller numbers of retrogradely labeled CGRPir neurons were also observed in the ventrolateral PB subnucleus, bilaterally with an ipsilateral predominance. These results suggest that CGRP may be a neuromodulator in the ascending visceral sensory pathways from the PB to the VPpc and the insular cortex, but not between the latter two structures.