The content of amino acids in the developing cerebellar cortex and deep cerebellar nuclei of granule cell deficient mutant mice.

Glutamic acid is the only free amino acid to be clearly reduced in mature granule cell deficient cerebellum. The correlation between concentration of glutamic acid and extent of granule cell loss suggests that it may serve as a neurotransmitter. Curiously, in two neurological mouse mutants, glutamic acid is also decreased in the deep cerebellar nuclei where there are no granule cells. We have now examined the amino acid content of cerebellar cortex and deep cerebellar nuclei of the granule cell deficient mutants, weaver and staggerer, during the postnatal period in which granule cell development takes place. We have found: (1) an early and transient deficit in taurine in weaver cerebellar cortex during the period of granule cell migration, (2) deficits during the second postnatal week in taurine, aspartic and glutamic acids in both weaver and staggerer cerebellar cortex, (3) that aspartic and glutamic acid deficits result from failure to increase concentrations at the normal rate after birth rather than from a fall from normal levels, (4) decreased concentrations of glutamic acid but not of taurine and aspartic acids apparent in the deep nuclei of both weaver and staggerer at about the same time as in cerebellar cortex, (5) amino acid changes in weaver heterozygote cerebellum which result in values intermediate in magnitude between normal and homozygous weaver animals and (6) an early and persistent reduction in staggerer deep nuclei of gamma-aminobutyric acid (GABA), the Purkinje cell transmitter, indicating early denervation or lack of full innervation of deep nuclei by Purkinje cells.