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Volume 16, Number 16, Issue of August 15, 1996 pp. 5141-5153
Copyright ©1996 Society for Neuroscience

Actions of Substance P on Rat Neostriatal Neurons In Vitro

Received Jan. 16, 1996; revised May 3, 1996; accepted May 21, 1996.

Toshihiko Aosaki and Yasuo Kawaguchi

Laboratory for Neural Circuits, Bio-Mimetic Control Research Center, The Institute of Physical and Chemical Research (RIKEN), Nagoya, Aichi 456, Japan

Actions of substance P (SP) on the neostriatal neurons in in vitro rat slice preparations were studied via whole-cell patch-clamp recording. Almost all large aspiny neurons (cholinergic cells) and half of the low-threshold spike (LTS) cells (somatostatin/NOS-positive cells) showed depolarization or an inward shift of the holding currents in response to bath-applied SP in a dose-dependent manner. In contrast, no responses were observed in fast-spiking (FS) cells (parvalbumin-positive cells) and medium spiny cells. Spike discharges followed by slow EPSPs/EPSCs were evoked by intrastriatal electrical stimulation in the large aspiny neurons. Pretreatment with [D-Arg¹,D-Pro²,D-Trp^7,9,Leu¹¹]-SP, an antagonist of the SP receptor, reversibly suppressed the induction of the slow EPSPs/EPSCs and unmasked slow IPSCs. The SP-induced inward current, although almost unchanged even after the blockade of I_h channels and voltage-dependent Na⁺, Ca²⁺, and K⁺ channels, changed its amplitude according to the Na⁺ concentration used in both the large aspiny neurons and LTS cells. Thus, the cation current could account for virtually all of the inward current at resting levels in both neurons. These results suggest that the firing of afferent neurons such as striatonigral medium spiny neurons, one of the possible sources of SP, would increase the firing probability of the two types of interneurons of the neostriatum by SP-receptor-mediated opening of tetrodotoxin-insensitive cation channels.

Key words: striatum; basal ganglia; cholinergic; somatostatin; interneurons; substance P; tachykinin; neuropeptide; cations; slice preparations; patch clamp

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