Microiontophoretic studies on the nature of the neurotransmitter in the subthalamo-entopeduncular pathway of the rat

Abstract

The aim of the present study was to determine the identity of the neurotransmitter released by the pathway from the subthalamic nucleus to the entopeduncular nucleus in the rat, using extracellular stimulating and recording techniques and microiontophoresis. In order to avoid stimulation of passing fibers at the level of the subthalamic nucleus, (collaterals to the entopeduncular nucleus of the caudato-nigral pathway, or direct projections to the entopeduncular nucleus from the substantia nigra or nucleus tegmenti pedunculopontinus), the experiments were performed in rats bearing chronic ipsilateral lesions in order to make these pathways degenerate. Under such conditions, subthalamic nucleus stimulation suppressed the spontaneous firing of all the entopeduncular nucleus cells studied (n = 40) for 15-25 ms (mean duration +/- S.E.M.:21.88 +/- 1.57 ms). Entopeduncular nucleus cells were identified by antidromic activation from the ventral anterior thalamic nucleus (40%) or lateral habenula nucleus (68%). Low doses of iontophoretically applied GABA (60 cells) or glycine (15 cells) were inhibitory upon entopeduncular cells, while acetylcholine or carbamylcholine were poorly excitatory (18 cells), or had no effect (28 cells). The subthalamic nucleus-evoked inhibition of entopeduncular neurons was reversed by microiontophoretically applied bicuculline or picrotoxin, at doses which blocked the GABA-induced response, but not that produced by glycine or acetylcholine. With similar experiments, strychnine and atropine were ineffective. This excludes a possible role of glycine or acetylcholine in the subthalamic-evoked inhibitory response of entopeduncular cells. The present study strongly suggest that GABA is a neurotransmitter in the inhibitory subthalamo-entopeduncular pathway.