Different populations of tyrosine-hydroxylase-immunoreactive neurons defined by differential expression of nitric oxide synthase in the human temporal cortex

In the mammalian neocortex, neurons containing tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis, constitute an enigmatic and ill-defined group of aspiny non-pyramidal cells. In the human neocortex, these neurons are mostly found in layers V-VI, the same layers in which another conspicuous group of nitrergic non-pyramidal cells are found - those containing nitric oxide synthase (nNOS) and that can be labeled by nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochemistry. The main aim of the present study was to determine the extent to which neurons and fibers containing TH, NADPHd or nNOS co-localize in the human temporal cortex, using immunocytochemistry and NADPHd histochemistry. Furthermore, we have quantified the degree to which axons immunoreactive (ir) for TH contact the somata of neurons by co-labeling with the neuron-specific nuclear protein NeuN. As a result, we show that the population of TH-ir neurons can be subdivided into two main neurochemical groups: those expressing nNOS (26%) and those that do not (74%). There was no co-localization of TH with nNOS in the prominent horizontally oriented plexus of fibers in layer I and we did not observe any double bouquet cells, chandelier cells or basket cells that contained TH. Finally, we observed that only 6% of the TH-ir axonal boutons examined (n = 1724) could be seen to contact neuronal somata. Thus, most TH-ir axons must form synapses with dendrites. In conjunction with data from previous studies, these results suggest that TH is found in different neurochemically defined subpopulations of non-pyramidal neurons in layers V-VI of the human temporal cortex. Consequently, it appears that a partial overlap of the catecholaminergic and nitrergic systems is probably due to the intrinsic cortical TH-nNOS-ir neurons.