Synaptic inputs to GABA_A and GABA_B receptors originate from discrete afferent neurons

γ-Aminobutyric acid (GABA) inhibits neurons by acting at GABA_A and GABA_B receptors but it is not known whether the two receptors are associated with discretely separate afferent inputs or whether GABA released from a single presynaptic neuron activates both receptors. Intracellular recordings were used to show that, in the lateral amygdala and ventral tegmental area of the rat, distinct sets of GABA-containing neurons provide the synaptic input to GABA_A and GABA_B receptors. Synaptic potentials resulting from GABA_A receptor activation (blocked by bicuculline) and from GABA_B receptor activation (blocked by 2-hydroxysaclofen) occurred spontaneously but as unrelated events. Furthermore, the two components of evoked synaptic potentials were differentially inhibited by agonists acting presynaptically (muscarine and 5-hydroxytryptamine). The finding that GABA acting at GABA_A and GABA_B receptors originates from distinct sets of presynaptic fibers suggests that two groups of GABA-containing neurons might be generally distinguishable in the mammalian nervous system.