GABA receptors constrain glutamate presynaptic release and postsynaptic actions in substantia gelatinosa of rat spinal cord.

The substantia gelatinosa (SG, lamina II of spinal cord gray matter) is pivotal for modulating nociceptive information from the peripheral to the central nervous system. γ-Aminobutyric acid type B receptors (GABARs), the metabotropic GABA receptor subtype, are widely expressed in pre- and postsynaptic structures of the SG. Activation of GABARs by exogenous agonists induces both pre- and postsynaptic inhibition. However, the actions of endogenous GABA via presynaptic GABARs on glutamatergic synapses, and the postsynaptic GABARs interaction with glutamate, remain elusive. In the present study, first, using in vitro whole-cell recordings and taking minimal stimulation strategies, we found that in rat spinal cord glutamatergic synapses, blockade of presynaptic GABARs switched "silent" synapses into active ones and increased the probability of glutamate release onto SG neurons; increasing ambient GABA concentration mimicked GABARs activation on glutamatergic terminals. Next, using holographic photostimulation to uncage glutamate on postsynaptic SG neurons, we found that postsynaptic GABARs modified glutamate-induced postsynaptic potentials. Taken together, our data identify that endogenous GABA heterosynaptically constrains glutamate release via persistently activating presynaptic GABARs; and postsynaptically, GABARs modulate glutamate responses. The results give new clues for endogenous GABA in modulating the nociception circuit of the spinal dorsal horn and shed fresh light on the postsynaptic interaction of glutamate and GABA.