Presynaptic impairment of cerebellar inhibitory synapses by an autoantibody to glutamate decarboxylase

Glutamic acid decarboxylase (GAD). the enzyme responsible for converting glutamate to gamma-aminobutyric acid (GABA), is a target of humoral autoimmunity in stiff-man syndrome and subacute: cerebellar ataxia. Recently, we found that an anti-GAD autoantibody in the CSF of an ataxic patient selectively suppressed GABA-mediated transmission on cerebellar Pukinje cells without affecting glutamate-mediated transmission. Here, we examine the mechanism by which the autoantibody impaired the inhibitory transmission, using immunohistochemistry and whole-cell recording in mt cerebellar slices. The present results indicate that CSF immunoglobulins prepared from an ataxic patient acted on the presynaptic terminals of GABAergic interneurons and decreased GABA release onto Purkinje cells. (C) 2000 Elsevier Science B.V. 411 rights reserved.