The Journal of Neurophysiology Vol. 84 No. 2 August 2000, pp. 1006-1011
Copyright ©2000 by the American Physiological Society

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

Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6, Canada

Chéry, Nadège and Yves De Koninck. GABA_B Receptors Are the First Target of Released GABA at Lamina I Inhibitory Synapses in the Adult Rat Spinal Cord. J. Neurophysiol. 84: 1006-1011, 2000. 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 GABA_A receptors (GABA_ARs) are expressed on the postsynaptic target, under certain conditions inhibitory events appeared to be mediated by GlyRs only. We therefore wanted to test whether GABA_B receptors could be activated in conditions where GABA released was insufficient to activate GABA_ARs. 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 GABA_AR component. PPD of small evoked IPSCs was not affected by the GABA_AR antagonist bicuculline but significantly attenuated by 10-30 µM CGP52432, a specific GABA_B receptor antagonist. These data indicate that, under conditions where GABA released is insufficient to affect postsynaptic GABA_ARs at lamina I inhibitory synapses, significant activation of presynaptic GABA_B receptors can occur.