Neurotensin innervation of the human cerebral cortex: lack of colocalization with catecholamines

We have localized neurotensin (NT) with immunocytochemical methods in the normal human cerebral cortex. Extensive areas of the frontal cortex, the hippocampal formation, and selected areas of the parietal, temporal and occipital lobes, were examined using post-mortem brain tissue. The peptidergic innervation was characteristically restricted to the limbic belt and to the dorsally contiguous regions. NT-labeled perikarya were found throughout the subiculum, including its dorsal supra-callosal continuation. NT terminal plexuses were particularly abundant in layers I-VI of the anterior cingulate cortex, in layer I of area 32 and of medical areas 9, 8, 6 and in layers II-III of area 29, of the presubiculum and entorhinal cortex. Elsewhere, NT fibers were scarce being more frequent in layer I. This regional and laminar pattern differed significantly from that of tyrosine hydroxylase (TH), which was used to label catecholaminergic axons, and preferentially the dopaminergic ones. Even in zones where TH and NT innervations were abundant, such as the anterior cingulate cortex or area 32, double-labeling procedures disclosed no colocalized fibers. The lack of NT-TH colocalization in human, contrasts with previous findings in the rodent cortex, where a contingent of the DA cortical afferents contains NT. The DA mesocortical neuronal population, labeled by TH antisera, thus seems to change its chemical phenotype, by losing the expression of an associated peptidergic neurotransmitter; this could be related to the predominant extension in the ascent of the phylogenetic scale of the non-colocalized, type of cortical DA innervation which is also found in rodents. The possible origins of the cortical, non-dopaminergic NT innervation in human are discussed: thalamo-cortical, subiculo-cortical or intrinsic. Such cortical NT innervation could be very important in limbic circuitry as a regulatory peptide in affective processes and could be involved in the physiology of pain and memory.