Decreased sensitivity of cerebellar nuclei neurons to GABA and taurine: effects of long-term inferior olive destruction in the rat.

The effects of iontophoretically applying the presumed Purkinje cell inhibitory neurotransmitters, GABA and taurine, were tested on neurons of the cerebellar nuclei in normal and in climbing-fiber-deafferented cerebella. Rats treated with 3-acetylpyridine to totally destroy the inferior olive were used for acute experiments 105-185 days after treatment. In controls, nearly all neuronal firing was dose-dependently depressed by both inhibitory amino acids. The depression in firing for both were antagonized by bicuculline and picrotoxin but not by strychnine while TAG specifically antagonized only responses to taurine. At sufficient doses, bicuculline and TAG induced disinhibitory responses (significant release of neuron discharge) in the absence of applied antagonist. In deafferented animals, the inhibitory efficacy of GABA and taurine were drastically reduced; most of the neurons failed to respond to these amino acids at the same iontophoretic parameters as for the control rats. Moreover, high doses of bicuculline and TAG did not induce any disinhibitory response (no significant increase in discharge rate) in most of the neurons tested. These results clearly demonstrate that climbing fiber deafferentation reduces postsynaptic sensitivity of the cerebellar nuclei neurons for the presumed Purkinje cell inhibitory neurotransmitters.