Role of GABA receptors in nitric oxide inhibition of dorsolateral periaqueductal gray neurons

Abstract

Nitric oxide (NO) affects neuronal activity of the midbrain periaqueductal gray (PAG). The purpose of this report was to investigate the role of GABA receptors in NO modulation of neuronal activity through inhibitory and excitatory synaptic inputs within the dorsolateral PAG (dl-PAG). First, spontaneous miniature inhibitory postsynaptic currents (mIPSCs) and excitatory postsynaptic currents (mEPSCs) were recorded using whole cell voltage-clamp methods. Increased NO by either S-nitroso-N-acetyl-penicillamine (SNAP, 100 μM) or L-arginine (50 μM) significantly augmented the frequency of mIPSCs of the dl-PAG neurons without altering their amplitudes or decay time constants. The effects were eliminated after bath application of carboxy-PTIO (NO scavenger), and 1-(2-trifluorom-ethylphenyl) imidazole (NO synthase inhibitor). In contrast, SNAP and L-arginine did not alter mEPSCs in dl-PAG neurons. However the frequency of mEPSCs was significantly increased with prior application of the GABA B receptors antagonist, CGP55845. In addition, NO significantly decreased the discharge rate of spontaneous action potentials in the dl-PAG neurons and the effect was reduced in the presence of the GABA A receptor antagonist, bicuculline. Our data show that within the dl-PAG NO potentiates the synaptic release of GABA, while NO-induced GABA presynaptically inhibits glutamate release through GABA B receptors. Overall, NO suppresses neuronal activity of the dl-PAG via a potentiation of GABAergic synaptic inputs and via GABA A receptors.

Fine-tuning of defensive behaviors in the dorsal periaqueductal gray by atypical neurotransmitters

“…Moreover, electrophysiological studies performed in dlPAG slices showed that NO can potentiate the synaptic release of GABA (48). …”

Involvement of NO-guanylyl cyclase pathway for the depression of spinal monosynaptic reflex by Mesobuthus tamulus venom in neonatal rat in vitro

“…This may be due to small quantity of NO generated (Garthwaite 2008). Similar to 5-HT, NO potentiates the synaptic release of GABA in the brain stem and midbrain (Wang et al 2007;Xing et al 2008). GABAergic and glycinergic inhibitory transmission in neonatal rat spinal cord has been demonstrated (Deshpande and Warnick 1988;Jha and Deshpande 2003;Warnick et al 1993).…”

“…5-HT, dopamine, glutamate, GABA etc. (Prast and Philippu 2001;Straub et al 2007;Xing et al 2008;Wang et al 2007). The NO-induced increase in 5-HT has been demonstrated and involves cGMP pathway (Prast and Philippu 2001).…”

Vesicular γ-aminobutyric acid transporter expression in rat periaqueductal gray matter

“…The close association of GATs and VGAT seems to be essential to promote GABA uptake from the neighborhood of its receptors, its restoration to presynaptic terminals, and transport to synaptic vesicles before a new release. GABA's inhibitory action could therefore be more potent in the dorsolateral PAG because of the simultaneous action of both types of GABA transporters and the presence of nitric oxide, which potentiates the synaptic release of GABA, which in turn reduces glutamate release through the GABA B receptors found in glutamatergic terminals [3,18]. Therefore, VGAT could be involved in the modulation of the behavioral and autonomic functions mediated by the dorsolateral PAG [19][20][21].…”