Effect of semicarbazide on electrical and metabolic activity of visual cortical and cerebellar neurons in tissue culture

The mechanism of the effect of semicarbazide, an inhibitor of glutamate decarboxylase, the enzyme involved in the synthesis of gamma-aminobutyric acid (GABA), on electrical and respiratory activity of Purkinje cells and cerebral cortical neurons of mice was investigated in tissue culture. The action of semicarbazide on the various parameters was shown to be biphasic in character: excitation followed by inhibition. The first phase could be connected with the blocking action of semicarbazide on glutamate decarboxylase synthesis. It is suggested that predominance of the excitatory background arising as a result of blockade of systems for which GABA is the transmitter, may lead to the development of lasting depolarization of the nerve cell membrane, giving rise to the secondary inhibitory effect. This substance was shown to have a stronger effect on Purkinje cells than on visual cortical neurons. This could indicate a high content of glutamate decarboxylase in the inhibitory synapses of cerebellar cells and could be indirect evidence of the presence of more active GABA synthesis in the cerebellum. A period of 10–14 days of development in culture during which the biphasic effect of semicarbazide was maximum was distinguished for both structures. It is suggested that inhibitory synapses for which GABA is the mediator are formed early during ontogenetic development in the brain structures studied.