LOCAL AND DIFFUSE SYNAPTIC ACTIONS OF GABA IN THE HIPPOCAMPUS

In the CNS, gamma-aminobutyric acid (GABA) acts as an inhibitory transmitter via ligand-gated GABA(A) receptor channels and G protein-coupled GABA(B) receptors. Both of these receptor types mediate inhibitory postsynaptic transmission in the hippocampus. In addition to these direct postsynaptic actions, GABA(B) receptor agonists inhibit excitatory transmission through presynaptic receptors on excitatory afferent terminals. However, a physiological role for the GABA(B) receptors on excitatory nerve endings has not been established. In this study, we have found a brief, heterosynaptic depression of excitatory synaptic transmission in the CA1 region of the hippocampal slice following short-lasting repetitive stimulation and determined that this inhibition is mediated by presynaptic GABA(B) receptors. The inhibition of GABA uptake greatly enhanced both the presynaptic action of GABA and the slow GABA(B)-mediated inhibitory postsynaptic current. Transmitter uptake was also found to regulate the ''spill-over'' of GABA at conventional GABA(A) synapses. These results suggest that uptake mechanisms restrict the spatial range of both point-to-point synaptic transmission mediated by GABA and its action at a distance.