Abstract
The periaqueductal gray (PAG) is involved in the central regulation of nociceptive transmission by affecting the descending inhibitory pathway. In the present study, we have addressed the functional role of presynaptic glycine receptors in spontaneous glutamatergic transmission. Spontaneous EPSCs (sEPSCs) were recorded in mechanically dissociated rat PAG neurons using a conventional whole-cell patch recording technique under voltage-clamp conditions. The application of glycine (100 µM) significantly increased the frequency of sEPSCs, without affecting the amplitude of sEPSCs. The glycine-induced increase in sEPSC frequency was blocked by 1 µM strychnine, a specific glycine receptor antagonist. The results suggest that glycine acts on presynaptic glycine receptors to increase the probability of glutamate release from excitatory nerve terminals. The glycine-induced increase in sEPSC frequency completely disappeared either in the presence of tetrodotoxin or Cd2+, voltage-gated Na+, or Ca2+ channel blockers, suggesting that the activation of presynaptic glycine receptors might depolarize excitatory nerve terminals. The present results suggest that presynaptic glycine receptors can regulate the excitability of PAG neurons by enhancing glutamatergic transmission and therefore play an important role in the regulation of various physiological functions mediated by the PAG.
Highlights
Glycine, in addition to GABA, is the primary inhibitory neurotransmitter in the brain stem and spinal cord
When these neurons were held at a VH of −60 mV using the whole-cell patch-clamp technique, the spontaneous inward synaptic currents were recorded in the presence of both 10 μM SR95531 and 50 μM APV, selective GABAA and NMDA, and receptor antagonists, respectively
The reversal potential for the spontaneous synaptic currents was estimated from the current-voltage relationship to be −2.5 mV. This value is very similar to the theoretical equilibrium potential of monovalent cations. These results indicate that the spontaneous synaptic events recorded from acutely isolated periaqueductal gray (PAG) neurons were AMPA/KA receptor-mediated Spontaneous EPSCs (sEPSCs)
Summary
In addition to GABA, is the primary inhibitory neurotransmitter in the brain stem and spinal cord. Functional roles of glycine receptors are largely unknown because glycine is unlikely to be released from presynaptic nerve terminals, and there is no direct evidence for glycinergic inhibitory postsynaptic currents in these brain structures (but see [6]). Glycine receptors are found in presynaptic nerve terminals of many brain regions, and their activation is known to facilitate neurotransmitter release from presynaptic nerve terminals [8,9,10,11]. In these cases, presynaptic glycine receptors might regulate the neuronal excitability in an indirect manner via the presynaptic modulation of neurotransmitter release
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