GABA(A) and GABA(B) receptors have opposite effects on synaptic glutamate release on the nucleus tractus solitarii neurons.

Cranial visceral afferent nerve transfers information about visceral organs to nucleus tractus solitarii (NTS) by releasing the excitatory neurotransmitter glutamate. Various endogenous modulators affect autonomic reflex responses by changing glutamatergic responses in the NTS. Although the expression of GABA(A) and GABA(B) receptors in glutamatergic terminals is known, their functional contribution on glutamate release is poorly characterized. Here, we used mechanically isolated NTS neurons to examine the mechanisms by which presynaptic GABA(A) and GABA(B) receptors modulate glutamatergic excitatory postsynaptic currents (EPSCs). EPSC were isolated by clamping voltage at equilibrium potential for chloride (-49 mV) without any GABA receptors antagonists. In all neurons, GABA(A) agonist, muscimol (1 and 10 μM), increased EPSC frequency (284.1±57% and 278.4±87% of control, respectively), but the GABA(B) agonist, baclofen (10 μM), decreased EPSC frequency (43±8% of control). The GABA(A) antagonist, gabazine (18 μM), decreased EPSC frequency in 50% of tested neurons, whereas GABA(B) antagonist, CGP (5 μM), increased the EPSC frequency in 36% of tested neurons. External application of GABA (1 and 30 μM) facilitating the EPSC frequency. The facilitation of the GABA(A) receptor-mediated release of glutamate was blocked by Na⁺-K⁺-Cl⁻ cotransporter type 1 antagonist or Na⁺ and Ca²⁺ channel inhibitors indicating GABA(A) presynaptic depolarization. Thus, tonically released GABA activates GABA(A) and GABA(B) receptors to modulate the release of glutamate. These findings provide cellular mechanisms of heterosynaptic GABA-glutamate integration of peripheral visceral afferent signals in the NTS.