Amino acid neurotransmitter candidates in rat cerebellum: Selective effects of kainic acid lesions

Kainic acid injections directly into the cerebellum destroy Purkinje, stellate, basket and Golgi II cells selectively with much less damage to granule cells. We have utilized such kainic acid lesions to evaluate the disposition of amino acid transmitter candidates in different neuronal populations of the cerebellum. Kainic acid lesions produce a 65-70% decrease in high affinity [³H]GABA uptake into synaptosomal fractions and a similar decrease in glutamic acid decarboxylase with a 50% reduction in endogenous GABA. Synaptosomal accumulation of [³H]glutamate and [³H]-aspartate is reduced 25-30% following such lesions while no decline in uptake of numerous other amino acids is observed. No significant changes are found in endogenous levels of glutamate, threonine, proline, alanine, valine, methionine, and isoleucine, while levels of glycine and serine are elevated following such lesions. These findings are consistent with the possibility that glutamate is the transmitter of granule cells and that GABA is the transmitter of the other cell types in the cerebellum.