Third group of neostriatofugal neurons: neurokinin B-producing neurons that send axons predominantly to the substantia innominata

Abstract

Neostriatal neurons that produce neurokinin B were investigated immunocytochemically in the rat brain with an antibody against the C-terminal portion of the precursor prepropeptide of neurokinin B, preprotachykinin B (PPTB). PPTB-immunoreactive neurons were scattered throughout the neostriatum and constituted 5.1% of neostriatal neurons. They were immunopositive for projection neuron markers, such as precursor peptides of substance P, enkephalins, and dynorphins, but negative for intrinsic neuron markers, suggesting that PPTB was expressed in neostriatal projection neurons. However, PPTB-immunoreactive neurons were immunonegative for dopamine- and cyclic AMP-regulated phosphoprotein, which is known to be produced by striatopallidal and striatonigral neurons. Furthermore, almost no PPTB-immunoreactive axon terminals were observed in the substantia nigra or globus pallidus. The authors then made large kainic acid lesions in the neostriatum to reveal the target areas of PPTB-producing neurons and observed a decrease in PPTB-immunoreactive fibers in the sublenticular portion of the substantia innominata and, to much lesser extent, in the bed nucleus of the stria terminalis and central nucleus of the amygdala. After injection of wheat germ agglutinin into the substantia innominata, PPTB immunoreactivity was detected in many retrogradely labeled neostriatal neurons. In contrast, no PPTB immunoreactivity was observed in striatonigral or striatopallidal neurons after injection of retrograde tracers into the substantia nigra or globus pallidus. Thus, neurokinin B-producing neostriatal neurons were considered to send projection fibers predominantly to the substantia innominata. Furthermore, PPTB-immunoreactive axonal swellings were closely apposed to neurokinin B receptor-immunoreactive dendrites in the substantia innominata. Overall, the present results indicate that the rat brain possesses a chemically and hodologically unique neostriatofugal pathway in addition to the direct and indirect pathways.