Tyrosine hydroxylase-producing neurons in the human cerebral cortex do not colocalize with calcium-binding proteins or the serotonin 3A receptor

Interneurons of the cerebral cortex play a significant role in cortical information processing and are of clinical interest due to their involvement in neurological disorders. In the human neocortex, three subsets of interneurons can be identified based on the production of the calcium-binding proteins parvalbumin, calretinin or calbindin. A subset of interneurons in the mouse cortex expresses the serotonin 3A receptor (5-HT3AR). Previous work in humans has also demonstrated the presence of a subgroup of cortical neurons that produces the catecholaminergic enzyme tyrosine hydroxylase (TH). Many TH-producing cells in the rat cortex coexpress calretinin and are adjacent to blood vessels. However, little is known about the phenotype of these TH interneurons in humans. Here we immunohistochemically examined the coexpression of TH with parvalbumin, calretinin, calbindin or 5-HT3AR in human Brodmann's areas 10 and 24, cortical regions with high densities of TH-containing neurons. Colocalization of TH with these calcium-binding proteins and with 5-HT3AR was not detected in either area. Cortical TH cells were rarely apposed to blood vessels, denoted by immunolabeling for the gliovascular marker aquaporin-4. Our results suggest that the TH-immunoreactive cells in the human cortex do not overlap with any known neurochemically-defined subsets of interneurons and provide further evidence of differences in the phenotype of these cells across species.