GABAB receptor (GABABR)
autoantibodies have been detected in the serum of
immunotherapy-responsive patients with
autoimmune encephalitis. This study aimed to investigate the effect of
immunoglobulin G (
IgG) from a patient with GABABR
antibodies on primary neuronal cultures and acute slices of entorhinal cortex. Primary hippocampal neuronal cultures were incubated with serum
immunoglobulin from patients with GABABR or
AMPA receptor (AMPAR)
antibodies for up to 72 h to investigate their effect on receptor surface expression. Whole-cell patch-clamp recordings from layer III pyramidal cells of the medial entorhinal cortex were used to examine the effect on neuronal activity. GABABR surface expression was unaltered by incubation with GABABR
antibodies. By contrast, after 24 h application of AMPAR
antibodies, AMPARs were undetectable. However, acute application of GABABR
IgG decreased both the duration of network UP states and the spike rate of pyramidal cells in the entorhinal cortex. GABABR
antibodies do not appear to affect GABABRs by internalization but rather reduce excitability on the medial temporal lobe networks. This unusual mechanism of action may be exploited in rational drug development strategies.