Elsevier

Brain Research

Volume 518, Issues 1–2, 4 June 1990, Pages 47-54
Brain Research

Excitatory influence of rat subthalamic nucleus to substantia nigra pars reticulata and the pallidal complex: electrophysiological data

https://doi.org/10.1016/0006-8993(90)90952-8Get rights and content

Abstract

By selective chemical stimulation of the subthalamic nucleus (STh) with the γ-aminobutyric acid (GABA) antagonist bicuculline, we have studied the effect of its projections to the target nuclei. Results show that bicuculline (0.39 mM) produced a mean activation of 358% in subthalamic neurons. Most of the cells recorded in the substantia nigra pars reticulata (SNpr), the entopenduncular nucleus (EP), and the globus pallidus (GP) were also significantly activated. In the substantia nigra pars compacta (SNpc), slight and opposite changes were produced: half of the cells were activated and half were inhibited. In the striatum, 3 types of responses were recorded: activation, inhibition, and biphasic effect. Inhibition of subthalamic neurons by local microinjection of muscimol (0.95 mM), produced reductions in the neuronal activity of cells in the SNpr, the EP, and the GP. These results suggest that the STh conveys an important and permanent excitatory influence onto its target nuclei. In another set of experiments, in order to investigate whether or not the STh utilizes glutamate for neurotransmission in the SNpr, we injected the glutamate receptor antagonist kynurenic acid (2.6 mM) into the SNpr, later followed by an injection of bicuculline in the STh. Kynurenic acid alone produced a mean inhibition of 30% in non-dopaminergic nigral cells, and antagonized the subsequent bicuculline-induced activating effect of the STh. These results further confirm recent data showing that the STh exerts an excitatory action on its efferent structures, and provide new evidence for glutamatergic transmission in subthalamic projections. In addition, they strongly suggest that this activation is the principal driving force contributing to the high level of spontaneous excitation observed in the EP and the SNpr, thus balancing the main inhibitory action of the striatum.

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      As part of the indirect pathway, the GPe projects to the output structures of the BG, the substantia nigra pars reticulata (SNr) and the internal segment of the globus pallidus (GPi) but also to the subthalamic nucleus (STN) and striatum. The cardinal input to the GPe is GABAergic inhibition from striatopallidal medium spiny neurons (MSNs) of the indirect pathway; however, the GPe is also reciprocally connected to the STN (Kita et al., 1983; Kita and Kitai, 1991; Robledo and Féger, 1990) and receives input from striatonigral MSNs (Cazorla et al., 2014; Kawaguchi et al., 1990; Wu et al., 2000). Thus, the GPe is positioned as a hub that connects the main BG pathways: the direct, indirect, and hyperdirect pathways (Mathai and Smith, 2011; Nambu et al., 2002).

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    Present address: Research Institute of Scripps Clinic, La Jolla, CA 92037, U.S.A.

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