MOSSY CELLS OF THE RAT DENTATE GYRUS ARE IMMUNOREACTIVE FOR CALCITONIN-GENE-RELATED PEPTIDE (CGRP)

The neuropeptide calcitonin gene-related peptide (CGRP) was localized in the hippocampus and dentate gyrus of the rat by immunocytochemistry at the light and electron microscopic levels. Without colchicine trea tment only faint neuropil labelling was found in the inner molecular l ayer of the dentate gyrus. Following colchicine treatment, a large num ber of neurons with numerous complex spines along the proximal dendrit es were visualized in the hilus of the dentate gyrus, particularly in the ventral areas, and, in addition, staining of the inner molecular l ayer became stronger. Several CA3c pyramidal cells located adjacent to the hilar region in the ventral hippocampus also appeared to be faint ly positive, although in most cases only their axon initial segments w ere labelled. Outside this region, the subicular end of the CA1 subfie ld contained occasional CGRP-positive nonpyramidal cells. The hilar CG RP-positive neurons were negative for parvalbumin, calretinin, cholecy stokinin and somatostatin, whereas most of them were immunoreactive fo r GluR2/3 (the AMPA-type glutamate receptor known to be expressed larg ely by principal cells). Correlated electron microscopy showed that th e spines along the proximal dendritic shafts indeed correspond to thor ny excrescences engulfed by large complex messy terminals forming asym metrical synapses. Pre-embedding immunogold staining demonstrated that CGRP immunoreactivity in the inner molecular layer was confined to ax on terminals that form asymmetrical synapses, and the labelling was as sociated with large dense-core vesicles. The present data provide dire ct evidence that CGRP is present in messy cells of the dentate gyrus a nd to a lesser degree in CA3c pyramidal cells of the ventral hippocamp us. These CGRP-containing principal cells terminate largely in the inn er molecular layer of the dentate gyrus, and may release the neuropept ide in conjunction with their 'classical' neurotransmitter, glutamate.