Abstract

Phasic and tonic inhibitions are two types of inhibitory activities involved in inhibitory processing in the CNS. In the spinal cord dorsal horn, phasic inhibition is mediated by both GABAergic and glycinergic inhibitory postsynaptic currents. In contrast to phasic inhibitory currents, using patch-clamp recording technique on spinal cord slices prepared from adult mice we revealed that tonic inhibitory currents were mediated by GABAA receptors but not by glycine receptors in dorsal horn lamina II region. We found that there was a linear relationship (r = 0.85) between the amplitude of tonic inhibitory currents and the frequency of GABAergic inhibitory postsynaptic currents. Analysis of charge transfer showed that the charges carried by tonic inhibitory currents were about 6 times of charges carried by phasic inhibitory currents. The prominent charge transfer by tonic inhibitory currents and their synaptic activity dependency suggest a significant role of tonic inhibition in sensory processing.

Highlights

  • GABA (γ-Aminobutyric acid) and glycine are two principle inhibitory neurotransmitters in the spinal cord dorsal horn

  • Under our voltage-clamp condition with cells being held at 0 mV, spontaneous inhibitory postsynaptic currents recorded from lamina II neurons were outward currents, and spontaneous excitatory postsynaptic currents were not detectable because the holding potential of 0 mV is at the reversal potential for sEPSCs

  • The baseline holding currents were -0.3 ± 0.5 pA (n = 6) in lamina II, not significantly different from the baseline noise level (Figure 1D). These results suggested that glycine receptors did not significantly account for the tonic inhibitory currents in dorsal horn lamina II neurons of adult mice

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Summary

Introduction

GABA (γ-Aminobutyric acid) and glycine are two principle inhibitory neurotransmitters in the spinal cord dorsal horn. They are either released separately or co-released from presynaptic terminals of inhibitory neurons. Upon the binding to GABAA receptors and glycine receptors at postsynaptic membrane, they elicit inhibitory postsynaptic currents (IPSCs). In addition to its action at synaptic sites, recent studies in several brain regions of matured animals have indicated that low concentrations of ambient GABA can activate high affinity GABAA receptors that are expressed at extrasynaptic sites to elicit a sustained inhibitory current [1,2,3,4,5]. For example tonic inhibitory currents were normally not observed in hippocampal pyramidal cells in brain slices from adult animals [[5,10], but see [11]]

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