Substance P Excites Large Aspiny Neurons of the Rat Neostriatum

Substance P (SP) is widely distributed in the mammalian central nervous system, where it is believed to play important roles as a neurotransmitter/neuromodulator. In the striatum, it has been reported that SP-containing fibers and terminals originate mainly from the striatonigral medium-sized spiny projection neurons (Bolam et al., 1986). Although the striatonigral pathway neurons were found to innervate both the pars reticulata of the substantia nigra (SNr) and the external segment of the globus pallidus (GPe), some of them also innervating the internal segment of the globus pallidus (GPi)/entopeduncular nucleus (EP) (Kawaguchi et al., 1990), in situ hybridization and immunohistochemical studies revealed that the receptor for SP, the NK1 receptor, is expressed only by the medium-sized somatostatinergic and large cholinergic interneurons of the striatum (Kaneko et al., 1993; Shigemoto et al., 1993; Aubry et al., 1994; Parent et al., 1995). How SP, released from the intrastriatal collaterals of the striatonigral medium-sized spiny neurons, affects these interneurons is an important question for the understanding of the function of the striatum, because they may in turn modulate the activities of the spiny projection neurons. However, no physiological evidence of such actions of SP has hitherto been available. Here, we report that SP excites the interneurons mainly by opening non-selective cation channels and discuss its functional significance.