Dynamics of AMPA receptors regulate epileptogenesis in patients with epilepsy

The excitatory glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) contribute to epileptogenesis. Thirty patients with epilepsy and 31 healthy controls are scanned using positron emission tomography with our recently developed radiotracer for AMPARs, [11C]K-2, which measures the density of cell-surface AMPARs. In patients with focal-onset seizures, an increase in AMPAR trafficking augments the amplitude of abnormal gamma activity detected by electroencephalography. In contrast, patients with generalized-onset seizures exhibit a decrease in AMPARs coupled with increased amplitude of abnormal gamma activity. Patients with epilepsy had reduced AMPAR levels compared with healthy controls, and AMPARs are reduced in larger areas of the cortex in patients with generalized-onset seizures compared with those with focal-onset seizures. Thus, epileptic brain function can be regulated by the enhanced trafficking of AMPAR due to Hebbian plasticity with increased simultaneous neuronal firing and compensational downregulation of cell-surface AMPARs by the synaptic scaling. [Display omitted] •We quantify levels of AMPARs in epilepsy patients and controls using PET tracer [11C]K-2•Increased AMPARs augment the amplitude of abnormal gamma activity•Cell-surface AMPARs are generally decreased in patients with epilepsy•Hebbian plasticity and homeostatic scaling regulate epileptic brain function Eiro et al. measure the density of cell-surface AMPARs in 30 epilepsy patients and 31 healthy controls with the PET tracer [11C]K-2. Increased cell surface AMPARs augment abnormal gamma activity, while patients with epilepsy generally exhibit reduced cell-surface AMPARs. Thus, Hebbian and homeostatic plasticity regulate epileptic brain function.