Neuropeptide-containing neurons of the cerebral cortex are also GABAergic

Neurons in the cat and monkey cerebral cortex were stained immunocytochemically for glutamic acid decarboxylase (GluDCase; L-glutamate 1-carboxy-lyase, EC 4.1.1.15), somatostatin (SRIF), neuropeptide Y (NPY), and cholecystokinin octapeptide (CCK). In all areas of cortex examined (somatic sensory, motor, parietal and visual areas), neurons displaying immunoreactivity for each of these molecules were nonpyramidal cells. Co-localization of GluDCase immunoreactivity with peptide immunoreactivity in the same cells was demonstrated by (i) the antibody elution method, staining the same cells by immunofluorescence, first for a peptide and then for GluDCase; (ii) double staining of the same sections with sheep anti-GluDCase and rabbit anti-peptide antisera, the bound antibodies being localized by rhodamine-conjugated donkey anti-sheep and fluorescein-conjugated swine anti-rabbit secondary antisera. With both procedures, cell bodies immunoreactive for GluDCase and for each of the peptides were found in all areas of cortex examined. With double labeling on single sections, it was found that all CCK-, SRIF-, and NPY-immunoreactive cells in cat cortex and 90%-95% in monkey cortex are also GluDCase positive. Many more cells, however, are immunoreactive for GluDCase alone. GluDCase was co-localized with CCK, SRIF, or NPY not only in cell somata, but also in small punctate structures, which are likely to be axon terminals. From the data gained in previous electron microscopic studies, we postulate that neurons displaying GluDCase- and CCK-like immunoreactivity are a class separate from those displaying GluDCase- and SRIF-like immunoreactivity. NPY, however, is co-localized with SRIF immunoreactivity. These results imply that classes of cortical interneuron contain a conventional neurotransmitter (γ-aminobutyric acid) and a neuromodulator (one of the peptides).