The immunocytochemical localization of substance P in the human striatum: a postmortem ultrastructural study

The striatum is a basal ganglia structure that is involved in motor, cognitive, and behavioral functions. In the striatum, the neuroactive peptide, substance P, is colocalized with GABA in the subset of medium spiny neurons that projects to the substantia nigra. Normal human striata (n = 5) obtained from the Maryland Brain Collection were processed for substance P immunoreactivity, prepared for electron microscopy, and analyzed using both stereology and simple profile counts. Most substance P-labeled neurons had a nonindented nucleus and a moderate amount of cytoplasm, typical of medium spiny projection neurons in other species. A small percentage (8%) of labeled neurons had indented nuclei, but otherwise had similar morphology. Synapses formed on labeled cell bodies were rare. Synapses formed by substance P-labeled axon terminals constituted 4.4% of the total synapses in the neuropil. Labeled terminals (1) formed synapses with both spines and dendrites with approximately equal frequency, (2) formed mostly symmetric synapses (76-85%), and (3) formed synapses predominantly with unlabeled (78%) profiles. Substance P-labeled spines varied in shape and comprised 37-42% of all spines forming synapses. In the caudate, the proportion of synapses with perforated postsynaptic densities was 55% on unlabeled vs. 45% on labeled spines, but in the putamen, this type of synapse was much more frequently present on unlabeled (73%) vs. labeled (27%) spines. These data describe substance P in the normal human striatum, which serve as comparative data to that of other species as well as normative data for further studies of brain disease that may involve striatal substance P neurons.