A novel postsynaptic group II metabotropic glutamate receptor role in modulating baroreceptor signal transmission

The nucleus tractus solitarius (NTS) is essential for orchestrating baroreflex control of blood pressure. When a change in blood pressure occurs, the information is transmitted by baroreceptor afferent fibers to the central network by glutamate binding to ionotropic glutamate receptors on second-order baroreceptor neurons. Glutamate also activates presynaptic group II and III metabotropic glutamate receptors (mGluRs), depressing both glutamate and GABA release to modulate baroreceptor signal transmission. Here we present a novel role for postsynaptic group II mGluRs to further fine-tune baroreceptor signal transmission at the first central synapses. In a brainstem slice with ionotropic glutamate and GABA receptors blocked, whole-cell patch-clamp recordings of second-order baroreceptor neurons revealed that two group II mGluR agonists evoked concentration-dependent membrane hyperpolarizations. The hyperpolarization remained when a presynaptic contribution was prevented with Cd(2+), was blocked by a postsynaptic intervention of intracellular dialysis of the G-protein signaling inhibitor, was mimicked by endogenous release of glutamate by tractus solitarius stimulation, and was prevented by a group II mGluR antagonist. Postsynaptic localization of group II mGluRs was confirmed by fluorescent confocal immunohistochemistry and light microscopy. Group II mGluR induced-currents consisted of voltage-dependent outward and inward components, prevented by tetraethylammonium chloride and tetrodotoxin, respectively. In contrast to group II mGluR-induced hyperpolarization, there was no effect on intrinsic excitability as determined by action potential shape or firing in response to depolarizing current injections. The data suggest a novel mechanism for postsynaptic group II mGluRs to fine-tune baroreceptor signal transmission in the NTS.