GABA | GABAA Receptor Plasticity in Epileptogenesis

Abstract

Retrospective studies suggest that precipitating events such as prolonged seizures, stroke, or trauma increase the risk of development of epilepsy later in life. Alterations in inhibitory neurotransmission have been proposed as one of the contributing factors in the development of epilepsy (epileptogenesis). γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mature brain and the GABA A receptor (GABAR) mediates most fast synaptic inhibition. Changes in GABAR subunit expression and function have been reported in adult animals beginning immediately after prolonged seizures (status epilepticus (SE)) and continuing through development of epilepsy. In the immature brain, however, GABA acts as an excitatory neurotransmitter and GABA receptor subunit expression is developmentally regulated. Further, early-life events such as SE elicit a pattern of GABAR plasticity in the immature brain that is distinct from the pattern seen in the adult brain. Identifying the GABAR changes that occur during epileptogenesis at different ages, and understanding the mechanisms that regulate these changes, will help identify new therapeutic targets for the prevention and treatment of acquired epilepsies.