Binding and uptake of putative neurotransmitters in mutant mouse cerebellum and cerebellar reaggregat

Abstract

γ-Amino butyric acid (GABA) appears to be the inhibitory transmitter of various cerebellar interneurons, while glutamate has been suggested as the excitatory transmitter of granule cells. In this study we have determined the developmental profile from day 2 to day 60 for the Naa-independent (presumably post-synaptic receptor) binding of [3H]GABA (Kd = 34 nM) and [3H]kainic acid, a glutamate analog (Kd = 53 nM. Both binding activities increase steadily to adult levels with kainic acid achieving this more rapidly. Cerebellar cells (7 day) cultured as reaggregates for 14 days showed an increase in GABA binding and glutamate uptake compared to the starting tissue but did not achieve the levels seen in vivo, while kainic acid binding and GABA uptake remained low. Binding and uptake measurements were performed in neurological mutants. Agranular mutants, weaver, reeler and staggerer demonstrated as expected, marked decreases in total GABA binding and glutamate uptake into synaptosomes, and to a lesser extent GABA uptake. In addition total kainate binding was depressed. In comparison, Purkinje cell degeneration mutants showed only a small decrease in kainic acid binding. These results suggest that kainic acid binding does not identify the post-synaptic glutamate receptor.