BRIDGING THE CLEFT AT GABA SYNAPSES IN THE BRAIN

A fragile balance between excitation and inhibition maintains the norm al functioning of the CNS. The dominant inhibitory, neurotransmitter o f the mammalian brain is GABA, which acts mainly through GABA(A) and G ABA(B) receptors. Small changes in GABA-mediated inhibition can alter neuronal excitability profoundly and, therefore, a wide range of compo unds that clearly modify GABA(A)-receptor function are used clinically as anesthetics or for the treatment of various nervous system disorde rs. Recent findings have started to unravel the operation of central G ABA synapses where inhibitory events appear to result from the synchro nous opening of only tens of GABA(A) receptors activated by a saturati ng concentration of GABA. Such properties of GABA synapses impose cert ain constraints on the physiological and pharmacological modulation of inhibition in the brain.