Few cortical cholecystokinin immunoreactive neurons have long projections.

Cholecystokinin (CCK)-like immunoreactive neurons have been reported to be widely distributed throughout both the neo- and allocortices. In the present study, we were interested in determining whether these cortical CCK neurons have long projections using the double-labeling technique of fluorescence retrograde tracing combined with immunofluorescence for CCK. The distribution of CCK immunoreactive perikarya and fibers was plotted throughout the rostro-caudal extent of the cerebral cortex in both untreated and colchicine-treated albino rats. In the double-labeling experiments, the animals received injections of fluorescent retrograde tracers into cortical, limbic, striatal or thalamic structures, followed one to two days later by colchicine treatment. Brains were subsequently processed for indirect immunofluorescence for CCK-octapeptide and fluorescent dye localization. It was found that 1) a small number of prefrontal cortical CCK neurons were double-labeled with both fluorescent dye and immunofluorescence for CCK after dye injection into midline thalamus, 2) only rarely were cortical CCK neurons double-labeled with injection of tracers into cortex, striatum, or other subcortical structures, 3) numerous midbrain CCK neurons were double-labeled after dye injection into prefrontal cortex and anterior cingulate cortex. and 4) colchicine or cannula injection damage to cortical forebrain tracts (corpus callosum, internal capsule, external capsule, anterior commissure) resulted in the appearance of numerous CCK immunoreactive fibers not normally seen in the undamaged tracts. Although the possibility remains that cortical CCK neurons may be refractory to transport of retrograde tracers, these results suggest that CCK-like immunoreactive neurons of the rat cerebral cortex are predominantly local circuit neurons and that only minor cortico-cortical and cortico-subcortical CCK-containing projections exist.