GABAA Receptors in Normal Development and Seizures: Friends or Foes?

Abstract

GABA(A) receptors have an age-adapted function in the brain. During early development, they mediate excitatory effects resulting in activation of calcium sensitive signaling processes that are important for the differentiation of the brain. In more mature stages of development and in adults, GABA(A) receptors transmit inhibitory signals. The maturation of GABA(A) signaling follows sex-specific patterns, which appear to also be important for the sexual differentiation of the brain. The inhibitory effects of GABA(A) receptor activation have been widely exploited in the treatment of conditions where neuronal silencing is necessary. For instance, drugs that target GABA(A) receptors are the mainstay of treatment of seizures. Recent evidence suggests however that the physiology and function of GABA(A) receptors changes in the brain of a subject that has epilepsy or status epilepticus.This review will summarize the physiology of and the developmental factors regulating the signaling and function of GABA(A) receptors; how these may change in the brain that has experienced prior seizures; what are the implications for the age and sex specific treatment of seizures and status epilepticus. Finally, the implications of these changes for the treatment of certain forms of medically refractory epilepsies and status epilepticus will be discussed.