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ABSTRACT: Our experiments demonstrate a novel role for group I metabotropic glutamate receptor (mGluR) subtypes 1 and 5 in generating a long-lasting synaptic excitation in the substantia gelatinosa (SG) and deep dorsal horn (DH) neurons of the rat spinal cord. In the present study we have investigated a slow excitatory postsynaptic current (EPSC), elicited by a brief high intensity (at Adelta/C fiber strength) and high frequency (20 or 100 Hz) stimulation of primary afferent fibers (PAFs) using whole-cell patch-clamp recordings from neurons located in the DH (laminae II-V) in spinal cord slices of young rats and wild-type and gene-targeted mice lacking mGluR1 subtype. The results shown here suggest that the activation of both mGluR1 and mGluR5 along with NK1 receptors, may be involved in the generation of the slow EPSC in the spinal cord DH. Inhibition of glial and neuronal glutamate transporters by DL-threo-beta-benzyloxyaspartate (TBOA) enhanced the group I mGluR-dependent slow EPSC about eightfold. Therefore, we conclude, that glutamate transporters strongly influence the group I mGluR activation by PAFs possibly at sensory synapses in the DH. Overall these data indicate that stimulus trains can generate a sustained and widespread glutamate signal that can further elicit prolonged EPSCs predominantly mediated by the group I mGluRs. These slow excitatory synaptic currents may have important functional implications for DH cell firing and synaptic plasticity of sensory transmission, including nociception.
Neuroscience 08/2008; 154(4):1372-87. · 3.38 Impact Factor
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Annals of the New York Academy of Sciences 12/2006; 448(1):385 - 402. · 3.15 Impact Factor
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ABSTRACT: The effects of group I metabotropic glutamate (mGlu) receptors on excitatory transmission in the rat dorsal horn, but mostly substantia gelatinosa, neurons were investigated using conventional intracellular recording in slices. The broad spectrum mGlu receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S, 3R-ACPD), the group I mGlu receptor selective agonist (S)-3, 5-dihydroxyphenylglycine (DHPG), and the selective mGlu subtype 5 agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), all induce long-lasting depression of A primary afferent fibers-mediated monosynaptic excitatory postsynaptic potential (EPSP), and long-lasting potentiation of polysynaptic EPSP, and EPSP in cells receiving C-afferent fiber input. The DHPG potentiation of polysynaptic EPSP was partially or fully reversed by (S)-4-carboxyphenylglycine (S-4CPG), the mGlu subtype 1 preferring antagonist. 2-Methyl-6-(phenylethynyl)-pyridine, the potent and selective mGlu subtype 5 antagonist, partially reversed the CHPG potentiation of polysynaptic EPSP. The effects of DHPG on monosynaptic and polysynaptic EPSPs were reduced, or abolished, by the N-methyl-D-aspartate (NMDA) receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (AP5). A clear and pronounced facilitation of the expression of DHPG- and CHPG-induced enhancement of polysynaptic EPSP, and EPSP evoked at C-fiber strength, was seen in the absence of gamma-aminobutyric acid subtype A receptor- and glycine-mediated synaptic inhibition. Besides dual modulation of excitatory synaptic transmission, DHPG induces depression of inhibitory postsynaptic potentials evoked by primary afferent stimulation in dorsal horn neurons. In addition, group I mGlu receptor agonists produced a direct persistent excitatory postsynaptic effect consisting of a slow membrane depolarization, an increase in input resistance, and an intense neuronal discharge. Cyclothiazide and (S)-4-CPG, the mGlu receptor subtype 1 preferring antagonists, significantly attenuated the DHPG-induced depolarization. These results demonstrate that the pharmacological activation of group I metabotropic glutamate receptors induces long-term depression (LTD) and long-term potentiation (LTP) of synaptic transmission in the spinal dorsal horn. These types of long-term synaptic plasticity may play a functional role in the generation of post-injury hypersensitivity (LTP) or antinociception (LTD).
Brain Research 01/2001; 887(2):359-77. · 2.73 Impact Factor
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Progress in brain research 02/2000; 129:115-34. · 3.04 Impact Factor
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ABSTRACT: The effect of DAMGO, a mu-opioid receptor agonist, on intracellular Ca2+ transients evoked by the application of NMDA, was studied in freshly dissociated neurons from the superficial dorsal horn in the spinal cord of young rats. DAMGO (5-10 microns) reduced the amplitude of the Ca2+ transients measured with Fura-2 to 58 +/- 17% of the controls in 41% of the neurons tested. The effect of DAMGO was dose dependent and reversible. The reduction of NMDA-induced Ca2+ transients by DAMGO was prevented by application of the opioid antagonists naloxone (0.1-5 microM) and CTAP (0.2-2 microM). DAMGO also reduced Ca2+ transients induced by high K+ in 29% of the neurons. These data suggest that mu-receptor activation regulates NMDA-induced Ca2+ transients in a complex manner, by reducing both a depolarization-induced component and the NMDA-channel component of this Ca2+ signal.
Neuroreport 10/1997; 8(14):3061-5. · 1.66 Impact Factor
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ABSTRACT: Impulses in primary afferent nerve fibers may produce short- or long-lasting modifications in spinal nociception. Here we have identified a robust long-term depression (LTD) of synaptic transmission in substantia gelatinosa neurons that can be induced by low-frequency stimulation of primary afferent Adelta-fibers. Synaptic transmission between dorsal root afferents and neurons in the substantia gelatinosa of the spinal cord dorsal horn was examined by intracellular recording in a transverse slice dorsal root preparation of rat spinal cord. Conditioning stimulation of dorsal roots with 900 pulses given at 1 Hz (10 V, 0.1 msec) produced LTD of EPSP amplitudes in substantia gelatinosa neurons to 41 +/- 10% of control that lasted for at least 2 hr. When A- and C-fibers were recruited, conditioning stimulation was as effective as A-fiber stimulation alone. After LTD, synaptic strength could be increased to its original level by applying a second, high-frequency tetanic stimulus to the dorsal root, indicating that LTD is reversible and not attributable to damage of individual synapses. Bath application of the GABAA receptor antagonist bicuculline and glycine receptor antagonist strychnine did not affect LTD. When NMDA receptors were blocked by bath application of D-2-amino-5-phosphonovaleric acid, LTD was abolished or strongly reduced. Loading substantia gelatinosa neurons with Ca2+ chelator BAPTA also blocked or reduced LTD. After incubation of slices with calyculin A, a selective and membrane permeable inhibitor of protein phosphatases 1 and 2A, LTD was not attenuated. We propose that this form of LTD may be relevant for long-lasting segmental antinociception after afferent stimulation.
Journal of Neuroscience 09/1997; 17(16):6483-91. · 7.11 Impact Factor
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ABSTRACT: 1. Here we report that in acutely isolated rat spinal dorsal horn neurons, the glycine receptor can be regulated by exogenous calcium/ calmodulin-dependent protein kinase II (CaM-KII). Intracellularly applied, the alpha-subunit of CaM-KII enhanced glycine receptor-activated current recorded with the use of the whole cell patch-clamp technique. This result suggests that the function of glycine receptor is modulated by CaM-KII, but the cellular mechanism underlying the enhancement of glycine receptor-activated current is still unknown.
Journal of Neurophysiology 07/1996; 75(6):2651-3. · 3.32 Impact Factor
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M Randić
Progress in brain research 02/1996; 113:463-506. · 3.04 Impact Factor
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ABSTRACT: This study examined the effects of selective activation of kappa 1-opioid receptors on excitatory transmission in substantia gelatinosa (SG) using intracellular recordings from SG neurons in transverse slices of the young rat lumbar spinal cord. Monosynaptic and polysynaptic excitatory postsynaptic potentials (EPSPs) were evoked by orthodromic electrical stimulation of A delta or C primary afferent fibers in the dorsal root after blocking inhibitory inputs with bicuculline and strychnine, NMDA receptors with D-2-amino-5-phosphonovaleric acid and mu- and delta-opioid receptors with CTAP and ICI 174,864, respectively. Bath application of dynorphin A1-17 or U-69, 593 caused dual modulation of the peak amplitude of presumed monosynaptic AMPA receptor-mediated EPSPs, decreasing synaptic potentials at nanomolar concentrations in a majority of SG cells examined (dynorphin, 63%; U-69,593, 91%), and increasing EPSPs at micromolar concentrations. Only the inhibitory action of dynorphin A1-17 was consistently and completely blocked by norbinaltorphimine (nor-BNI). Since U-69,593 and nor-BNI are selective for the kappa 1-opioid receptors, the depression of EPSPs is likely to be mediated by the kappa1-opioid receptors. Under conditions of blockade of synaptic transmission with TTX and mu-and delta-opioid receptors, dynorphin A1-17 and U-69,593 hyperpolarize most of SG neurons and decrease their membrane input resistance, the finding suggesting that direct interaction of kappa-agonists with a postsynaptic receptor is likely explanation for the inhibition of EPSPs. However, in some SG cells, the inhibition of EPSPs appears to be of presynaptic origin since dynorphin A1-17 and U-69,593 did depress the EPSPs in the absence of changes in passive membrane properties. Rp-cAMPS, a membrane permeant potent competitive inhibitor of cAMP-activated protein kinase, prevented the depressant effect of dynorphin A 1-17. This finding suggested a possibility that dynorphin A1-17, acting through a decrease in intracellular cyclic AMP levels, can reduce the synaptic responses of SG neurons. These results provide the first electrophysiological demonstration that the activation of kappa 1-opioid receptors inhibits AMPA receptor-mediated primary afferent neurotransmission in the substantia gelatinosa of the young rat spinal cord. This effect may mediate the ability of kappa-receptor agonists to produce antinociception.
Journal of Neuroscience 11/1995; 15(10):6809-26. · 7.11 Impact Factor
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ABSTRACT: 1. Here we report that in acutely isolated rat spinal dorsal horn neurons, the gamma-aminobutyric acid-A (GABAA) receptor can be regulated by calcium/calmodulin-dependent protein kinase II (CaM-KII). Intracellularly applied, the alpha-subunit of CaM-KII enhanced GABAA-receptor-activated current recorded with the use of the whole cell patch-clamp technique. This effect was associated with reduced desensitization of GABA responses. 2. GABA-induced currents are also potentiated by calyculin A, an inhibitor of protein phosphatases 1 and 2A. 3. Conventional intracellular recordings were made from hippocampal CA1 neurons in slices to determine the effect of intracellular application of CaM-KII on inhibitory synaptic potentials evoked by electrical stimulation of the stratum oriens/alveus. The inhibitory synaptic potential was enhanced by CaM-KII; this mechanism may contribute to long-term enhancement of inhibitory synaptic transmission and may also play a role in other forms of plasticity in the mammalian brain.
Journal of Neurophysiology 06/1995; 73(5):2099-106. · 3.32 Impact Factor
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ABSTRACT: In freshly isolated spinal dorsal horn (DH) neurons (laminae I-IV) of the young rat, the effects of dynorphin A1-17, U-50,488H and U-69,593 on inward currents induced by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) were studied under whole-cell voltage-clamp conditions. When the cells were clamped to a holding potential of -60 mV, co-application of dynorphin A1-17 (10(-6) M) and AMPA (2 x 10(-5) M) reversibly decreased the peak amplitude of the initial transient component of the AMPA-induced current in 72% of the examined cells. In addition, dynorphin (10 microM) in perforated patch-recordings consistently produced a decrease in the steady-state component of the AMPA response. The depressant effect was concentration-dependent (IC50 = 86 nM) and reversible. The dynorphin A1-17-induced depression of the AMPA response was associated with slowing of the response kinetics, including both a 10-90% rise-time and time constant of decay. The AMPA-induced currents were modulated by dynorphin not only during the co-administration but also after the removal of the peptide. Dynorphin increased the initial peak AMPA current in 42% of the examined cells. Similar as with dynorphin A1-17, the peak amplitude of the AMPA-induced current was reversibly suppressed in the presence of 1 microM U-50,488H and U-69,593 in 75% and 86% of the examined cells, respectively. Naloxone and the kappa 1-selective antagonist norbinaltorphimine (nor-BNI) blocked the initial depressant but not late excitatory effects of dynorphin A1-17 and U-50,488H. This antagonistic effect of naloxone and norbinaltorphimine suggests that the depressant effect of dynorphin A1-17 on the AMPA-activated conductance is a true opioid, probably kappa 1-opioid receptor-mediated event. In contrast, the dynorphin-induced late potentiation of AMPA/KA responses appears to be a non-opioid effect since it was not inhibited by nor-BNI, CTAP and naltrindole, the selective kappa-, mu- and delta-opioid receptor blocking agents, respectively. Pretreatment of DH neurons with pertussis toxin blocked the depressant action of dynorphin A1-17, indicating that a Gi- or Go-type G protein was required for this effect on AMPA-activated currents. Intracellular dialysis with a highly specific peptide inhibitor (peptide 6-22) of the cAMP-activated protein kinase (PKA), and with Rp-cAMPS, prevented the depressant effect of dynorphin A1-17. In addition, staurosporine, a nonselective kinase inhibitor, blocked the dynorphin depression of the AMPA response.(ABSTRACT TRUNCATED AT 400 WORDS)
Brain Research 03/1995; 671(2):227-44. · 2.73 Impact Factor
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Progress in brain research 02/1995; 104:225-53. · 3.04 Impact Factor
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ABSTRACT: 1. Here we report that in acutely isolated rat spinal dorsal horn (DH) neurons, the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)/kainate and N-methyl-D-aspartate (NMDA) receptors can be regulated by endogenous and exogenous calcium/calmodulin-dependent protein kinase II (CaM-KII). Intracellularly applied, the alpha-subunit of CaM-KII enhanced AMPA/kainate and NMDA currents recorded with the use of the whole cell patch-clamp technique. 2. Microcystin, a nonselective phosphatases inhibitor, also enhances AMPA and NMDA responses. 3. Conventional intracellular recordings were made from substantia gelatinosa neurons in spinal cord slices to determine the effect of intracellular application of CaM-KII on excitatory synaptic potentials evoked by electrical stimulation of primary afferent fibers. Excitatory synaptic transmission was enhanced by CaM-KII, which is consistent with the importance of phosphorylation of the postsynaptic AMPA/kainate and NMDA receptor-ion complexes in the short- and long-term changes in synaptic transmission.
Journal of Neurophysiology 12/1994; 72(5):2525-31. · 3.32 Impact Factor
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ABSTRACT: Whole-cell voltage-clamp technique was used to examine the effects of a mu-opioid receptor agonist DAGO (Tyr-D-Ala-Gly-Me-Phe-Gly-ol-enkephalin) on GABA-induced currents in acutely isolated spinal dorsal horn (DH) neurons from laminae I-IV of young rats. We found that a bicuculline-sensitive GABA-induced current was potentiated by DAGO (0.5-500 nM), in a dose-dependent manner, in approximately 62% of the tested cells. The elevated GABA responses outlasted the period of DAGO application, and either recovered within 10 min after the removal of the peptide or persisted for up to 50 min. The potentiating effect of DAGO was reduced or prevented by naloxone and the mu-opioid receptor-selective antagonist beta-funaltrexamine. A similar enhancing effect on the membrane currents activated by administration of muscimol, a GABAA receptor-specific agonist, was produced by DAGO. In addition, a transient depression of GABA responses was observed in approximately 25% of the cells tested. These results indicate that the mu-opioid agonist DAGO modulates the sensitivity of postsynaptic GABAA receptors in a large proportion of spinal neurons from laminae I-IV, with the major effect being facilitation. The DAGO action could contribute to the regulation of the strength of primary afferent neurotransmission, including nociception.
Neuroscience Letters 11/1994; 180(2):109-13. · 2.11 Impact Factor
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ABSTRACT: Synaptic transmission between dorsal root afferents and neurons in the superficial laminae of the spinal dorsal horn (laminae I-III) was examined by intracellular recording in a transverse slice preparation of rat spinal cord. Brief high-frequency electrical stimulation (300 pulses at 100 Hz) of primary afferent fibers produced a long-term potentiation (LTP) or a long-term depression (LTD) of fast (monosynaptic and polysynaptic) EPSPs in a high proportion of dorsal horn neurons. Both the AMPA and the NMDA receptor-mediated components of synaptic transmission at the primary afferent synapses with neurons in the dorsal horn can exhibit LTP and LTD of the synaptic responses. In normal and neonatally capsaicin-treated rats, the induction of LTP requires the activation of NMDA receptor-gated conductances. The induction of LTP or LTD, however, was not abolished in the presence of bicuculline, a GABAA receptor antagonist. The results demonstrate that distinct and long-lasting modulation in synaptic efficiency can be induced at primary afferent synapses with neurons in the superficial laminae of spinal dorsal horn by high-frequency stimulation of dorsal root afferents and that these changes may be physiologically relevant for transmission and integration of sensory information, including pain.
Journal of Neuroscience 01/1994; 13(12):5228-41. · 7.11 Impact Factor
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ABSTRACT: Glutamate-gated ion channels mediate excitatory synaptic transmission in the central nervous system and are involved in synaptic plasticity, neuronal development and excitotoxicity (5,24). These ionotropic glutamate receptors were classified according to their preferred agonists as AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid), KA (kainate), and NMDA (N-methyl-D-aspartate) receptors [Trends Pharmacol. Sci., 11 (1990) 25-33]. The present study of NMDA receptor channels expressed in acutely isolated spinal dorsal horn (DH) neurons of young rat reveals that they are subject to modulation through the adenylate cyclase cascade. Whole-cell voltage-clamp recording mode was used to examine the effect of adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase (PKA) on the responses of DH neurons to NMDA. Whole-cell current response to NMDA was enhanced by 8 Br-cAMP, a membrane permeant analog of cAMP or by intracellular application of cAMP or catalytic subunit of PKA.
Neuroscience Letters 11/1993; 161(2):124-8. · 2.11 Impact Factor
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ABSTRACT: Intracellular recordings were made from rat dorsal horn neurons in the in vitro slice preparation to study the actions of cyclic adenosine 3',5'-monophosphate (cyclic AMP). In the presence of TTX, bath application of the membrane permeable analogue of cyclic AMP, 8-Br cyclic AMP (25-100 microM) caused a small depolarization of the resting membrane potential accompanied by a variable change in membrane input resistance. In addition, 8-Br cyclic AMP caused a long-lasting increase in the spontaneous synaptic activity and the amplitude of presumed monosynaptic excitatory postsynaptic potentials evoked in the substantia gelatinosa neurons by orthodromic stimulation of a lumbar dorsal root. When the fast voltage-sensitive Na conductance was blocked by TTX, 8-Br cyclic AMP enhanced in a reversible manner, the depolarizing responses of a proportion of dorsal horn neurons to N-methyl-D-aspartic acid (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), quisqualic acid (QA) and kainic acid (KA). The effects of 8-Br cyclic AMP on the resting membrane potential and the NMDA response of dorsal horn neurons were mimicked by reducing phosphodiesterase activity with bath application of 3-isobutyl-1-methylxanthine, but not by cyclic AMP applied extracellularly. Moreover, we have found that intracellular application of a protein inhibitor of cyclic AMP-dependent protein kinase (PKI) into dorsal horn neurons prevents the 8-Br cyclic AMP-induced potentiation of the NMDA response of these cells. These results suggest that in the rat spinal dorsal horn the activation of the adenylate cyclase-cyclic AMP-dependent protein kinase system may be involved in the enhancement of the sensitivity of postsynaptic excitatory amino acid (NMDA, AMPA, KA) receptors and modulation of primary afferent neurotransmission, including nociception.
Brain Research 12/1992; 596(1-2):111-23. · 2.73 Impact Factor
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ABSTRACT: The actions of a gamma-aminobutyric acid B (GABAB) agonist, (-)-baclofen, on the electrophysiological properties of neurons and synaptic transmission in the spinal dorsal horn (laminae I-IV) were examined by using intracellular recordings in spinal cord slice from young rats. In addition, the effects of baclofen on the dorsal root stimulation-evoked outflow of glutamate and aspartate from the spinal dorsal horn were examined by using high performance liquid chromatography (HPLC) with flourimetric detection. Superfusion of baclofen (5 nM to 10 microM) hyperpolarized, in a stereoselective and bicuculline-insensitive manner, the majority (86%) of tested neurons. The hyperpolarization was associated with a decrease in membrane resistance and persisted in a nominally zero-Ca2+, 10 mM Mg(2+)- or a TTX-containing solution. Our findings indicate that the hyperpolarizing effect of baclofen is probably due to an increase in conductance to potassium ions. Baclofen decreased the direct excitability of dorsal horn neurons, enhanced accommodation of spike discharge, and reduced the duration of Ca(2+)-dependent action potentials. Baclofen depressed, or blocked, excitatory postsynaptic potentials evoked by electrical stimulation of the dorsal roots. Spontaneously occurring synaptic potentials were also reversibly depressed by baclofen. Whereas baclofen did not produce any consistent change in the rate of the basal outflow of glutamate and aspartate, the stimulation-evoked release of the amino acids was blocked. The present results suggest that baclofen, by activating GABAB receptors, may modulate spinal afferent processing in the superficial dorsal horn by at least two mechanisms: (1) baclofen depresses excitatory synaptic transmission primarily by a presynaptic mechanism involving a decrease in the release of excitatory amino acids, and (2) at higher concentrations, the hyperpolarization and increased membrane conductance may contribute to the depressant effect of baclofen on excitatory synaptic transmission in the rat spinal dorsal horn.
Brain Research 11/1991; 562(2):265-75. · 2.73 Impact Factor
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ABSTRACT: In a rat spinal slice preparation the participation of excitatory amino acid (EAA) receptors in the responses of deep dorsal horn neurons to repetitive stimulation of lumbar dorsal roots was investigated using 3 EAA receptor antagonists, kynurenic acid, D-(-)-2-amino-4-phosphonovaleric acid (D-APV) and 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (CNQX) and current-clamp and voltage-clamp techniques. We found that the slow excitatory synaptic response evoked by 10-20 Hz electrical stimulation of primary afferent fibers consisted of two depolarizing components: an initial component lasting 1-5 s and a late one of 1-3 min duration. The initial and late components of the slow excitatory synaptic response can also be distinguished on the basis of their voltage-dependence and sensitivity to Mg2+ ions, kynurenate, D-APV and CNQX. In the presence of Mg2+, the initial component of the slow excitatory synaptic response increased with membrane hyperpolarization, whereas the late component decreased in most of the cells examined. In a zero-Mg2+ medium, the initial component was potentiated, but the late component was reduced. In both transverse and longitudinal spinal cord slices perfused with 1.2 mM Mg(2+)-containing medium, bath application of kynurenic acid (0.1-0.5 mM), D-APV (0.05-0.1 mM) and CNQX (5-7 microM) caused a reversible reduction of the peak amplitude of the initial slow depolarizing component that was greater in transverse (kynurenic acid: by 92.6 +/- 5.0%; D-APV: by 69.1 +/- 7.8%; CNQX: by 76.6 +/- 9.8%) than in longitudinal slices (kynurenic acid: by 53.3 +/- 1.3%; D-APV: by 31.5 +/- 9.1%; CNQX: by 35.3 +/- 11.1%). In contrast, all 3 antagonists of EAA receptors produced no consistent change in the peak amplitude or half-duration of the late depolarizing component of the slow excitatory synaptic response. Our results obtained with EAA receptor antagonists, at resting membrane potentials, in the absence and presence of Mg2+ and synaptic inhibition, indicate that the synaptic activation of the NMDA- and non-NMDA-receptor systems of deep spinal dorsal horn neurons by repetitive stimulation of primary afferent fibers may be selectively involved in the mediation of the initial, but not the late depolarizing component of the slow excitatory synaptic response.
Brain Research 11/1991; 561(2):236-51. · 2.73 Impact Factor
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ABSTRACT: Possible correlation of release of endogenous glutamate (Glu) and aspartate (Asp) with stimulation parameters used to activate primary sensory neurons was examined using the rat spinal cord slice--dorsal root ganglion preparation and high performance liquid chromatography with fluorimetric detection. Selective activation of the low-threshold (A beta) primary afferent fibers resulted in a two-fold increase in the rate of basal outflow of Asp and a smaller increase in the outflow of Glu from the rat spinal dorsal horn slices into the superfusing medium. The activation of both the low (A beta)- and the high-threshold (A delta + C) primary afferents elicited also a significant increase in the outflow of Asp and Glu relative to control. Glu and Asp are released in significant amounts following superfusion of the dorsal root ganglia with capsaicin or resiniferatoxin. DAGO (Tyr-D-Ala-Gly-MePhe-Gly-ol-enkephalin), an agonist at mu-opioid receptors, attenuated the high-intensity stimulation-evoked outflow of Asp and Glu in a naloxone-sensitive manner. Our results have provided further evidence in support of the contention that Glu and Asp act as excitatory synaptic transmitters in the spinal dorsal horn. A role for mu-opioid receptors in modulation of spinal processing of somatosensory information is indicated.
Brain Research 08/1991; 553(2):347-52. · 2.73 Impact Factor
