CALCITONIN-GENE-RELATED PEPTIDE (CGRP) IN THE CAT NEOCORTEX - EVIDENCE FOR A SPARSE BUT WIDESPREAD NETWORK OF IMMUNOREACTIVE FIBERS

The morphology, and laminar and topographic distribution of fibers con taining calcitonin gene-related peptide (CGRP) immunoreactivity were s tudied by light and electron microscopic methods in the cerebral corte x of adult cats using a rabbit antiserum raised against the C-terminal region of the rat alpha-CGRP. At the light microscopic level, a spars e number of CGRP-positive fibers were observed in the frontal, parieta l, and occipital cortices. They showed numerous irregularly spaced var icosities, were mostly oriented vertically, and in rare cases gave ris e to boutons terminaux as they ascended toward the pial surface. At th e border between layers I and II, they branched into horizontal fibers that could be followed for several hundred microns in layer I and gav e rise to terminal clusters of boutons. In some sections, CGRP-positiv e fibers were seen in close association with blood vessels. At the ele ctron microscopic level, CGRP immunoreactivity was found in axon termi nals containing few mitochondria and clear synaptic vesicles. CGRP-pos itive axon terminals were very sparse, and mainly of small size. The m ajority 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 densit y and the occipital cortex the lowest. These results show that CGRP-co ntaining axons are more widely distributed than previously thought sin ce they were observed in all the cortical areas examined, and cast som e doubts on the hypothesis that the functional role of this peptide is restricted to the processing of visceral sensory information. Based o n the topographic and laminar distribution, the ultrastructural featur es of immunoreactive axon terminals, and the results of previous studi es on the distribution of CGRP in the rat thalamus, it is proposed tha t the thalamic intralaminar nuclei may be the most likely, though not the only, source of the CGRP innervation of the cerebral cortex and th at CGRP may exert a modulatory action on cortical neurons.