Time course of GABA in the synaptic clefts of inhibitory synapses in the rostral nucleus of the solitary tract

Concentration and time course of neurotransmitter in the synaptic cleft determines the amplitude and the duration of the resulting postsynaptic current. However, technical limitations involved in monitoring the time course of neurotransmitter concentration in the extra-cellular space have prevented direct evaluation of factors that influence neurotransmitter level in the cleft. Tetanic stimulation results in saturation of postsynaptic GABA(A) receptors in the rostral nucleus of the solitary tract (rNST) and GABA diffusion defines the decay time course of the inhibitory potentials or currents (IPSP/Cs). By applying a GABA concentration-response curve to these data it is possible to calculate the GABA concentration transient in the clefts of rNST inhibitory synapses. The analysis indicates that tetanic stimulation produces a GABA concentration that exceeds the concentration of neurotransmitter required to activate all postsynaptic GABA(A) receptors, resulting in short-term modification of the IPSP/Cs decay time. Moreover, the results also demonstrate that the rate of diffusion of GABA from the synaptic cleft is defined by two exponentials. A mathematical model of this process has been developed that supports these conclusions.