The morphology, and laminar and topographic distribution of fibers containing calcitonin gene-related peptide (CGRP) immunoreactivity were studied by light and electron microscopic methods in the cerebral cortex of adult cats using a rabbit antiserum raised against the C-terminal region of the rat a-CGRP.

At the light microscopic level, a sparse number of CGRP-positive fibers were observed in the frontal, parietal, and occipital cortices. They showed numerous irregularly spaced varicosities, were mostly oriented vertically, and in rare cases gave rise to boutons ter-minaux as they ascended toward the pial surface. At the border between layers I and II, they branched into horizontal fibers that could be followed for several hundred microns in layer I and gave rise to terminal clusters of boutons. In some sections, CGRP-positive fibers were seen in close association with blood vessels. At the electron microscopic level, CGRP immunoreactivity was found in axon terminals containing few mitochondria and clear synaptic vesicles. CGRP-positive axon terminals were very sparse, and mainly of small size. The majority formed conventional synapses, all of the asymmetric type. CGRP-positive fibers showed an uneven topographic distribution through the cortical mantle, with the frontal areas exhibiting the highest density and the occipital cortex the lowest.

These results show that CGRP-containing axons are more widely distributed than previously thought since they were observed in all the cortical areas examined, and cast some doubts on the hypothesis that the functional role of this peptide is restricted to the processing of visceral sensory information. Based on the topographic and laminar distribution, the uttrastructural features of immunoreactive axon terminals, and the results of previous studies on the distribution of CGRP in the rat thalamus, it is proposed that the thalamic intralaminar nuclei may be the most likely, though not the only, source of the CGRP innervation of the cerebral cortex and that CGRP may exert a modulatory action on cortical neurons.

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