Inhibitory postsynaptic currents recorded from motoneurons viewed in thin slices of the rat spinal cord

1988 ◽  
Vol 7 ◽  
pp. S168
Author(s):  
Tomoyuki Takahashi
Keyword(s):  
Spinal Cord ◽  
Rat Spinal Cord ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Thin Slices

Actions of Midazolam on GABAergic Transmission in Substantia Gelatinosa Neurons of Adult Rat Spinal Cord Slices

2000 ◽  
Vol 92 (2) ◽  
pp. 507-507 ◽  
Author(s):  
Tatsuro Kohno ◽  
Eiichi Kumamoto ◽  
Hiroshi Baba ◽  
Toyofumi Ataka ◽  
Manabu Okamoto ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Benzodiazepine Receptor ◽  
Substantia Gelatinosa ◽  
Rat Spinal Cord ◽  
Gabaergic Transmission ◽  
Gaba A ◽  
Inhibitory Postsynaptic Currents ◽  
Adult Rat ◽  
Postsynaptic Currents ◽  
Adult Rat Spinal Cord

Background Although intrathecal administration of midazolam has been found to produce analgesia, how midazolam exerts this effect is not understood fully at the neuronal level in the spinal cord. Methods The effects of midazolam on either electrically evoked or spontaneous inhibitory transmission and on a response to exogenous gamma-aminobutyric acid (GABA), a GABA(A)-receptor agonist, muscimol, or glycine were evaluated in substantia gelatinosa neurons of adult rat spinal cord slices by using the whole-cell patch-clamp technique. Results Bath-applied midazolam (1 microM) prolonged the decay phase of evoked and miniature inhibitory postsynaptic currents (IPSCs), mediated by GABA(A) receptors, without a change in amplitudes, while not affecting glycine receptor-mediated miniature inhibitory postsynaptic currents in both the decay phase and the amplitude. Either GABA- or muscimol-induced currents were enhanced in amplitude by midazolam (0.1 microM) in a manner sensitive to a benzodiazepine receptor antagonist, flumazenil (1 microM); glycine currents were, however, unaltered by midazolam. Conclusions Midazolam augmented both the duration of GABA-mediated synaptic current and the amplitude of GABA-induced current by acting on the GABA(A)-benzodiazepine receptor in substantia gelatinosa neurons; this would increase the inhibitory GABAergic transmission. This may be a possible mechanism for antinociception by midazolam.

Giant, TTX-insensitive, inhibitory postsynaptic currents in cultured rat spinal cord and medullary neurons

1996 ◽  
Vol 76 (5) ◽  
pp. 3341-3350 ◽  
Author(s):  
C. A. Lewis ◽  
D. S. Faber
Keyword(s):  
Spinal Cord ◽  
Amplitude Ratio ◽  
Mean Amplitude ◽  
Prolonged Release ◽  
Whole Cell ◽  
Mean Values ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Order Of Magnitude ◽  
Medullary Neurons

1. In whole cell patch-clamp studies on cultured rat embryonic spinal cord and medullary neurons bathed in tetrodotoxin, DL-2-amino-5-phosphonovaleric acid, and 6-cyano-7-nitroquinoxaline-2,3-dione, large and long-lasting spontaneous inhibitory postsynaptic currents were occasionally recorded. The amplitudes of these events were 1 order of magnitude larger than those of spontaneous miniature inhibitory postsynaptic currents. Because these large currents had reduced amplitudes in calcium-free saline and in solutions containing glycinergic or GABAergic antagonists, we conclude that they were probably produced by large and prolonged release of glycine and/or 4-amino-n-butyric acid (GABA), which subsequently bind to their postsynaptic receptors. 2. The frequency of spontaneous miniature postsynaptic currents increased dramatically during the long, slow decay phase of these large postsynaptic currents. Considering the requirement for extracellular calcium for the occurrence of these large responses, we hypothesize that this increased frequency reflected an increased intracellular calcium concentration in the presynaptic terminal. 3. Similar evidence for large inhibitory postsynaptic currents and prolonged transmitter release was observed in cell-attached patches, which also exhibited the smaller, spontaneous miniature inhibitory postsynaptic currents, suggesting that these large events are properties of single synaptic terminals. 4. A comparison of the properties of these large inhibitory postsynaptic currents recorded in whole cell mode or cell-attached patches showed no statistically significant differences. The overall mean values, then, are 13.9 +/- 1.6 (SE) ms and 4.5 +/- 0.5 s for the 10-90% rise time and duration, respectively. Furthermore, these large events had amplitudes that were 11-fold larger than the mean amplitude of the miniatures (i.e., mean amplitude ratio of 10.8 +/- 0.5). 5. Periodic large increases in the frequency of spontaneous miniature inhibitory postsynaptic currents occurred in both cell-attached patches and in the whole cell mode, and these increases were only sometimes associated with the large inhibitory postsynaptic currents. The rhythmicity in both recording configurations had similar temporal characteristics, with average interburst intervals of 5 and 12–14 s. Presumably these bursts of spontaneous miniature postsynaptic currents reflected periodic oscillations in the Ca2+ concentration in presynaptic terminals. 6. Both the probability and the frequency of occurrence of large inhibitory postsynaptic currents doubled during the 7-day period of time in culture when experiments were performed, suggesting that these large currents may play a role during development.

Norepinephrine Facilitates Inhibitory Transmission in Substantia Gelatinosa of Adult Rat Spinal Cord (Part 2)

2000 ◽  
Vol 92 (2) ◽  
pp. 485-485 ◽  
Author(s):  
Hiroshi Baba ◽  
Peter A. Goldstein ◽  
Manabu Okamoto ◽  
Tatsuro Kohno ◽  
Toyofumi Ataka ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Patch Clamp ◽  
Dorsal Horn ◽  
Dynamic Range ◽  
Spinal Cord Dorsal Horn ◽  
Substantia Gelatinosa ◽  
Inhibitory Interneurons ◽  
Patch Clamp Technique ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents

Background It has been reported previously that norepinephrine, when applied to the spinal cord dorsal horn, excites a subpopulation of dorsal horn neurons, presumably inhibitory interneurons. In the current study, the authors tested whether norepinephrine could activate inhibitory interneurons, specifically those that are "GABAergic." Methods A transverse slice was obtained from a segment of the lumbar spinal cord isolated from adult male Sprague-Dawley rats. Whole-cell patch-clamp recordings were made from substantia gelatinosa neurons using the blind patch-clamp technique. The effects of norepinephrine on spontaneous GABAergic inhibitory postsynaptic currents were studied. Results In the majority of substantia gelatinosa neurons tested, norepinephrine (10-60 microM) significantly increased both the frequency and the amplitude of GABAergic inhibitory postsynaptic currents. These increases were blocked by tetrodotoxin (1 microM). The effects of norepinephrine were mimicked by the alpha1-receptor agonist phenylephrine (10-80 microM) and inhibited by the alpha1-receptor-antagonist WB-4101 (0.5 microM). Primary-afferent-evoked polysynaptic excitatory postsynaptic potentials or excitatory postsynaptic currents in wide-dynamic-range neurons of the deep dorsal horn were also attenuated by phenylephrine (40 microM). Conclusion The observations suggest that GABAergic interneurons possess somatodendritic alpha1 receptors, and activation of these receptors excites inhibitory interneurons. The alpha1 actions reported herein may contribute to the analgesic action of intrathecally administered phenylephrine.

Norepinephrine Facilitates Inhibitory Transmission in Substantia Gelatinosa of Adult Rat Spinal Cord (Part 1)

2000 ◽  
Vol 92 (2) ◽  
pp. 473-473 ◽  
Author(s):  
Hiroshi Baba ◽  
Koki Shimoji ◽  
Megumu Yoshimura
Keyword(s):  
Spinal Cord ◽  
Substantia Gelatinosa ◽  
Gamma Aminobutyric Acid ◽  
Sprague Dawley ◽  
Patch Clamp Technique ◽  
Membrane Hyperpolarization ◽  
Nociceptive Transmission ◽  
Inhibitory Postsynaptic Currents ◽  
Adult Rat ◽  
Postsynaptic Currents

Background The activation of descending norepinephrine-containing fibers from the brain stem inhibits nociceptive transmission at the spinal level. How these descending noradrenergic pathways exert the analgesic effect is not understood fully. Membrane hyperpolarization of substantia gelatinosa (Rexed lamina II) neurons by the activation of alpha2 receptors may account for depression of pain transmission. In addition, it is possible that norepinephrine affects transmitter release in the substantia gelatinosa. Methods Adult male Sprague-Dawley rats (9-10 weeks of age, 250-300 g) were used in this study. Transverse spinal cord slices were cut from the isolated lumbar cord. The blind whole-cell patch-clamp technique was used to record from neurons. The effects of norepinephrine on the frequency and amplitude of miniature excitatory and inhibitory postsynaptic currents were evaluated. Results In the majority of substantia gelatinosa neurons tested, norepinephrine (10-100 microM) dose-dependently increased the frequency of gamma-aminobutyric acid (GABA)ergic and glycinergic miniature inhibitory postsynaptic currents; miniature excitatory postsynaptic currents were unaffected. This augmentation was mimicked by an alpha1-receptor agonist, phenylephrine (10-60 microM), and inhibited by alpha1-receptor antagonists prazosin (0.5 microM) and 2-(2,6-dimethoxyphenoxyethyl) amino-methyl-1,4-benzodioxane (0.5 microM). Neither postsynaptic responsiveness to exogenously applied GABA and glycine nor the kinetics of GABAergic and glycinergic inhibitory postsynaptic currents were affected by norepinephrine. Conclusion These results suggest that norepinephrine enhances inhibitory synaptic transmission in the substantia gelatinosa through activation of presynaptic alpha1 receptors, thus providing a mechanism underlying the clinical use of alpha1 agonists with local anesthetics in spinal anesthesia.

Development of Spontaneous Synaptic Transmission in the Rat Spinal Cord

1998 ◽  
Vol 79 (5) ◽  
pp. 2277-2287 ◽  
Author(s):  
Bao-Xi Gao ◽  
Gong Cheng ◽  
Lea Ziskind-Conhaim
Keyword(s):  
Spinal Cord ◽  
Action Potential ◽  
Synaptic Transmission ◽  
Inhibitory Synapses ◽  
Lumbar Spinal Cord ◽  
Rat Spinal Cord ◽  
Action Potential Firing ◽  
Quantal Release ◽  
Postsynaptic Currents ◽  
Potential Firing

Gao, Bao-Xi, Gong Cheng, and Lea Ziskind-Conhaim. Development of spontaneous synaptic transmission in the rat spinal cord. J. Neurophysiol. 79: 2277–2287, 1998. Dorsal root afferents form synaptic connections on motoneurons a few days after motoneuron clustering in the rat lumbar spinal cord, but frequent spontaneous synaptic potentials are detected only after birth. To increase our understanding of the mechanisms underlying the differentiation of synaptic transmission, we examined the developmental changes in properties of spontaneous synaptic transmission at early stages of synapse formation. Spontaneous postsynaptic currents (PSCs) and tetrodotoxin (TTX)-resistant miniature PSCs (mPSCs) were measured in spinal motoneurons of embryonic and postnatal rats using whole cell patch-clamp recordings. Spontaneous PSC frequencies were higher than mPSC frequencies in both embryonic and postnatal motoneurons, suggesting that even at embryonic stages, when action-potential firing rate was low, presynaptic action potentials played an important role in triggering spontaneous PSCs. After birth, the twofold increase in spontaneous PSC frequency was attributed to an increase in action-potential–independent quantal release rather than to a higher rate of action-potential firing. In embryonic motoneurons, the fluctuations in peak amplitude of spontaneous PSCs were normally distributed around single peaks with modal values similar to those of mPSCs. These data indicated that early in synapse differentiation spontaneous PSCs were primarily composed of currents generated by quantal release. After birth, mean mPSC amplitude increased by 50% but mean quantal current amplitude did not change. Synchronous, multiquantal release was apparent in postnatal motoneurons only in high-K+ extracellular solution. Comparison of the properties of miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs) demonstrated that mean mEPSC frequency was higher than mIPSC frequency, suggesting that either excitatory synapses outnumbered inhibitory synapses or that the probability of excitatory transmitter release was higher than the release of inhibitory neurotransmitters. The finding that mIPSC duration was several-fold longer than mEPSC duration implied that despite their lower frequency, inhibitory currents could modulate motoneuron synaptic integration by shunting incoming excitatory inputs for prolonged time intervals.

Action of Isoflurane on the Substantia Gelatinosa Neurons of the Adult Rat Spinal Cord

2005 ◽  
Vol 102 (2) ◽  
pp. 379-386 ◽  
Author(s):  
Ayako Wakai ◽  
Tatsuro Kohno ◽  
Tomohiro Yamakura ◽  
Manabu Okamoto ◽  
Toyofumi Ataka ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Rat Spinal Cord ◽  
Excitatory Postsynaptic Currents ◽  
Inhibitory Transmission ◽  
Adult Rat ◽  
Postsynaptic Currents ◽  
Acid Type ◽  
Adult Rat Spinal Cord

Background Although isoflurane, a volatile anesthetic, can block the motor response to noxious stimulation (immobility and analgesia) and suppress autonomic responsiveness, how it exerts these effects at the neuronal level in the spinal cord is not fully understood. Methods The effects of a clinically relevant concentration (1 rat minimum alveolar concentration [MAC]) of isoflurane on electrically evoked and spontaneous excitatory/inhibitory transmission and on the response to exogenous administration of the gamma-aminobutyric acid type A receptor agonist muscimol were examined in lamina II neurons of adult rat spinal cord slices using the whole cell patch clamp technique. The effect of isoflurane on the action potential-generating membrane property was also examined. Results Bath-applied isoflurane (1.5%, 1 rat MAC) diminished dorsal root-evoked polysynaptic but not monosynaptic excitatory postsynaptic currents. Glutamatergic miniature excitatory postsynaptic currents were also unaffected by isoflurane. In contrast, isoflurane prolonged the decay phase of evoked and miniature gamma-aminobutyric acid type A receptor-mediated inhibitory postsynaptic currents and increased the amplitude of the muscimol-induced current. Isoflurane had little effect on action potential discharge activity. Conclusions Isoflurane augments gamma-aminobutyric acid-mediated inhibitory transmission, leading to a decrease in the excitability of spinal dorsal horn neurons. This may be a possible mechanism for the antinociceptive effect of isoflurane in the spinal cord.

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