Effects of GABAB receptor antibodies on neuronal signalling and hippocampal function

GABA_B receptor limbic encephalitis with memory dysfunction and severe seizures is the most common subtype of autoimmune encephalitis with antibodies to a G protein-coupled receptor (GPCR). We will investigate the pathophysiology induced by anti-GABA_B receptor antibodies. In primary neurons and human induced pluripotent stem cells (iPSC) differentiated to neurons we will apply patch-clamp recordings and super-resolution microscopy to unravel functional and morphological changes in synapses exposed to anti-GABA_B receptor antibodies. In hippocampal slices of mice after intraventricular passive-transfer of GABA_B receptor antibodies we will analyze synaptic plasticity and network oscillations. In this mouse model we will further determine seizure susceptibility and epileptic activity. With these experiments, we expect to clarify the pathogenic role of anti-GABA_B receptor antibodies and we aim to identify clues for targeted therapeutic intervention.

Prof. Dr. Christian Geis

Prof. Dr. Dietmar Schmitz