Glutamic acid: Selective depletion by viral induced granule cell loss in hamster cerebellum

Cerebellar hypoplasia in the hamster induced by rat virus strain PRE 308 was used as a model system in which greater than 95% of the cerebellar granule cell population can be selectively depleted at an early stage of development. Electron microscopic examination of infected hamster cerebella indicated a significant reduction of parallel fiber synapses and granule cell dendrites in glomeruli. All other cell types occurred in approximately normal numbers and formed proper synaptic connections. To attempt to identify the transmitter of the cerebellar granule cell, we examined the uptakes of amino acids and amines into synaptosomes in the cerebella of hamsters with granuloprival cerebellar hypoplasia and their littermate controls. The high affinity uptakes of glutamic and aspartic acids were reduced by 70% in infected animals. No significant reductions occurred in the uptakes of a variety of other amino acids, putative neurotransmitters and their precursors. Endogenous glutamic acid was decreased by 43%, although endogenous protein concentration was not altered. Analysis of the free cerebellar amino acid content of infected animals revealed a selective decrease in glutamic acid and no decrease in other amino acids, in particular aspartic acid. Partial granule cell depletions were also produced and the extent of granule cell loss correlated with the decrease in endogenous glutamic acid and high affinity glutamic acid uptake. Granule cells are excitatory in function; the neurophysiologic action of glutamic acid is also excitatory. Our findings suggest that glutamic acid is the natural neurotransmitter of the cerebellar granule cell.