Dual impairment of GABAA- and GABAB-receptor-mediated synaptic responses by autoantibodies to glutamic acid decarboxylase

Abstract Anti-glutamate decarboxylase autoantibodies (GAD-A) are associated with a group of patients with progressive cerebellar ataxia. We reported previously that cerebellar GABA A -mediated synaptic transmission was presynaptically depressed by GAD-A in the cerebrospinal fluid (CSF). Using whole-cell recording of rat cerebellar slices, we found in the present study that CSF immunoglobulins from ataxic patients reduced gamma-aminobutyric acid (GABA) release from cerebellar interneurons, thereby attenuating presynaptic inhibition on neighboring excitatory synapses through GABA B receptors (GABA B Rs). Our results suggest that in in vitro slices, GAD-A elicited the pathophysiological action of reduction in GABA release, which subsequently resulted in dual synaptic impairment in the cerebellar circuit, by depression of GABA A receptor (GABA A R)-mediated inhibitory synaptic transmissions, and attenuation of GABA B receptor-mediated inhibition of excitatory transmissions.