The expression of neurokinin-1 receptor at striatal and pallidal levels in normal human brain

To further our knowledge of the site of action of substance P (SP) in the human basal ganglia, we applied single- and double-antigen localization methods to human postmortem tissue to compare the distribution of SP and its high affinity receptor neurokinin-1 (NK1R) at striatal and pallidal levels. The human striatum was found to harbor numerous heterogeneously distributed aspiny neurons that expressed NK1R. Most of them were of small size, but a moderate number of large-sized neurons and a small number of medium-sized neurons also expressed NK1R. The medium-sized NK1R-positive neurons coexpressed parvalbumin and appear to represent a hitherto unknown striatal interneuron. The three types of striatal NK1R-positive neurons were preferentially localized in the peripheral region of the striosomes, which were identified by their intense immunostaining for the limbic system-associated membrane protein. Numerous NK1R expressing neurons also occurred in both external (GPe) and internal (GPi) segments of the globus pallidus, as well as in the ventral pallidum (GPv). There was a marked decreasing rostrocaudal gradient in the number of these neurons in the GPe, but not in the GPi. A multitude of smooth and highly branched SP-immunoreactive fibers pervaded the entire pallidal complex and some of these fibers were in close contact with NK1R-positive neurons in the GPi, as well as in the rostral portion of the GPe. The latter result reveals that the so-called 'direct' striatofugal pathway provides SP-immunoreactive collaterals to the GPe, a finding that is at odd with the current model of basal ganglia organization.