GABAB Receptors Are the First Target of Released GABA at Lamina I Inhibitory Synapses in the Adult Rat Spinal Cord

Abstract

We have previously provided functional evidence that glycine and GABA are contained in the same synaptic vesicles and coreleased at the same synapses in lamina I of the rat spinal dorsal horn. However, whereas both glycine receptors (GlyRs) and GABAA receptors (GABAARs) are expressed on the postsynaptic target, under certain conditions inhibitory events appeared to be mediated by GlyRs only. We therefore wanted to test whether GABAB receptors could be activated in conditions where GABA released was insufficient to activate GABAARs. Focal stimulation in the vicinity of visually identified lamina I neurons elicited monosynaptic IPSCs in the presence of ionotropic glutamate receptor antagonists. Pairs of stimuli were given at different interstimulus intervals (ISI), ranging from 25 ms to 1 s to study the depression of the second of evoked IPSCs (paired pulse depression; PPD). Maximal PPD of IPSCs was 60 ± 14% (SE) (of the conditioning pulse amplitude), at ISI between 150 and 200 ms. PPD was observed with IPSCs evoked at stimulus intensities where they had no GABAAR component. PPD of small evoked IPSCs was not affected by the GABAAR antagonist bicuculline but significantly attenuated by 10–30 μM CGP52432, a specific GABAB receptor antagonist. These data indicate that, under conditions where GABA released is insufficient to affect postsynaptic GABAARs at lamina I inhibitory synapses, significant activation of presynaptic GABABreceptors can occur.