Autoradiographic localization of inhibitory and excitatory amino acid neurotransmitter receptors in human normal and olivopontocerebellar atrophy cerebellar cortex

Abstract

We used standard techniques of receptor autoradiography to study the distribution of inhibitory and excitatory amino acid neurotransmitter receptors in human normal cerebellar cortex. Benzodiazepine (BDZ) receptor density was relatively high in both granule cell and molecular layers. GABA A receptor density was highest in granule cell layer with lower receptor density in molecular layer. There was a lower density of GABA B receptors than GABA A receptors in both molecular and granule cell layers with a relatively higher density of GABA B receptors in molecular layer than in granule cell layer. In granule cell layer, the density of theN-methyl- d-aspartate (NMDA) subtype of excitatory amino acid receptors was greatest whereas in molecular layer the quisqualate (QA) receptor subtype density was greatest. With[ 3H]N-(1-[2-thienyl]cyclohexyl)3–4-piperidine as a ligand, there was no specific binding to the phencyclidine receptor. Molecular layer was also characterized by relatively high density of a non-NMDA/non-QA displaceable glutamate binding site. We studied also the cerebellar cortex of 4 cases of olivopontocerebellar atrophy (OPCA), a syndrome in which Purkinje and granule cells degenerate. In these specimens, there was significant decrement of BDZ and GABA A receptors in both molecular and granule cell layers, with loss of GABA B receptors in molecular layer. NMDA receptors were depleted in granule cell layer while QA receptors and the non-NMDA/non-QA glutamate binding site were significantly depleted in molecular layer. Our normal human and OPCA data are largely consistent with animal data about the cellular localization of cerebellar cortical amino acid neurotransmitter receptors.