Electrophysiological and pharmacological studies of the inhibitory projection from the cerebellar cortex to the deep cerebellar nuclei in tissue culture

Abstract In explant cultures of mouse cerebellum, short latency inhibitions can be recorded from neurones in the deep cerebellar nuclei after electrical stimulation in the cortical region. The responsible projection appears to originate from Purkinje cells and to be monosynaptic to cells in deep nuclei. In many cases, the inhibition is followed by a rebound excitation which has been attributed to a disinhibition. Known blockers of synaptic inhibition (bicuculline, bicuculline methiodide, picrotoxin and strychnine) were added to the perfusing solution, for study of their effects on the evoked inhibition and on depressions of activity by iontophoretically applied glycine and γ-aminobutyrate. The results indicate that γ-aminobutyrate is probably the transmitter responsible for the synaptic inhibition. The experiments demonstrate the reproducibility of a central nervous system pathway in tissue culture and the ease of pharmacological manipulation of such a model system. The model has promising applicability for the study of synaptic mechanisms and as a test substrate for the interaction of drugs with a γ-aminobutyrate mediated pathway, particularly where the study of such substances is difficult in vivo.