The effects of hydrogen ion on spinal neurons

1980 ◽  
Vol 58 (6) ◽  
pp. 650-655 ◽  
Author(s):  
K. C. Marshall ◽  
I. Engberg
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Neuronal Excitability ◽  
Input Resistance ◽  
Hydrogen Ion ◽  
Intracellular Recordings ◽  
Spinal Neurons ◽  
Number Of Cells

The effects of iontophoretically applied hydrogen ion (H+) on neuronal excitability were studied in the spinal cord of cats. The activity of extracellularly recorded neurons of the dorsal horn was either depressed or enhanced by H+ and in most cases of enhancement there was a preceding phase of depression. During intracellular recordings from motoneurons it was found that H+ application usually caused a hyperpolarization accompanied by an increase in cell input resistance. In a smaller number of cells the hyperpolarization was succeeded by a depolarization that was coupled with a decrease in input resistance. In some neurons it was shown that the depolarizing phase was more prominent and had a shorter latency when larger currents were used to eject H+. The varied reports from earlier studies of excitation or inhibition of neuronal excitability by H+ may be in part explainable by our observations that the effects may depend on the concentrations of H+ used.

scholarly journals Electrical maturation of spinal neurons in the human fetus: comparison of ventral and dorsal horn

2015 ◽  
Vol 114 (5) ◽  
pp. 2661-2671 ◽  
Author(s):  
M. A. Tadros ◽  
R. Lim ◽  
D. I. Hughes ◽  
A. M. Brichta ◽  
R. J. Callister
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Neuronal Excitability ◽  
Sensory Information ◽  
Input Resistance ◽  
Spinal Neurons ◽  
Nociceptive Information ◽  
The Central Nervous System ◽  
Patch Clamp Electrophysiology ◽  
In Utero Development

The spinal cord is critical for modifying and relaying sensory information to, and motor commands from, higher centers in the central nervous system to initiate and maintain contextually relevant locomotor responses. Our understanding of how spinal sensorimotor circuits are established during in utero development is based largely on studies in rodents. In contrast, there is little functional data on the development of sensory and motor systems in humans. Here, we use patch-clamp electrophysiology to examine the development of neuronal excitability in human fetal spinal cords (10–18 wk gestation; WG). Transverse spinal cord slices (300 μm thick) were prepared, and recordings were made, from visualized neurons in either the ventral (VH) or dorsal horn (DH) at 32°C. Action potentials (APs) could be elicited in VH neurons throughout the period examined, but only after 16 WG in DH neurons. At this age, VH neurons discharged multiple APs, whereas most DH neurons discharged single APs. In addition, at 16–18 WG, VH neurons also displayed larger AP and after-hyperpolarization amplitudes than DH neurons. Between 10 and 18 WG, the intrinsic properties of VH neurons changed markedly, with input resistance decreasing and AP and after-hyperpolarization amplitudes increasing. These findings are consistent with the hypothesis that VH motor circuitry matures more rapidly than the DH circuits that are involved in processing tactile and nociceptive information.

scholarly journals Metabotropic glutamate receptor 5 regulates excitability and Kv4.2-containing K+ channels primarily in excitatory neurons of the spinal dorsal horn

2011 ◽  
Vol 105 (6) ◽  
pp. 3010-3021 ◽  
Author(s):  
Hui-Juan Hu ◽  
Robert W. Gereau
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Neuronal Excitability ◽  
Gabaergic Neurons ◽  
Erk Signaling ◽  
Metabotropic Glutamate ◽  
Dorsal Horn Neurons ◽  
Spinal Dorsal ◽  
Excitatory Neurons

Metabotropic glutamate (mGlu) receptors play important roles in the modulation of nociception. Previous studies demonstrated that mGlu5 modulates nociceptive plasticity via activation of ERK signaling. We have reported recently that the Kv4.2 K+ channel subunit underlies A-type currents in spinal cord dorsal horn neurons and that this channel is modulated by mGlu5-ERK signaling. In the present study, we tested the hypothesis that modulation of Kv4.2 by mGlu5 occurs in excitatory spinal dorsal horn neurons. With the use of a transgenic mouse strain expressing enhanced green fluorescent protein (GFP) under control of the promoter for the γ-amino butyric acid (GABA)-synthesizing enzyme, glutamic acid decarboxylase 67 (GAD67), we found that these GABAergic neurons express less Kv4.2-mediated A-type current than non-GAD67-GFP neurons. Furthermore, the mGlu1/5 agonist, (R,S)-3,5-dihydroxyphenylglycine, had no modulatory effects on A-type currents or neuronal excitability in this subgroup of GABAergic neurons but robustly modulated A-type currents and neuronal excitability in non-GFP-expressing neurons. Immunofluorescence studies revealed that Kv4.2 was highly colocalized with markers of excitatory neurons, such as vesicular glutamate transporter 1/2, PKCγ, and neurokinin 1, in cultured dorsal horn neurons. These results indicate that mGlu5-Kv4.2 signaling is associated with excitatory dorsal horn neurons and suggest that the pronociceptive effects of mGlu5 activation in the spinal cord likely involve enhanced excitability of excitatory neurons.

Presynaptic and Interactive Peptidergic Modulation of Reticulospinal Synaptic Inputs in the Lamprey

2000 ◽  
Vol 83 (5) ◽  
pp. 2497-2507 ◽  
Author(s):  
David Parker
Keyword(s):  
Spinal Cord ◽  
Brain Stem ◽  
Peptide Yy ◽  
Input Resistance ◽  
Ventral Root ◽  
Interactive Effects ◽  
Inhibitory Effects ◽  
Spinal Neurons ◽  
Root Responses ◽  
The Brain

The modulatory effects of neuropeptides on descending inputs to the spinal cord have been examined by making paired recordings from reticulospinal axons and spinal neurons in the lamprey. Four peptides were examined; peptide YY (PYY) and cholecystokinin (CCK), which are contained in brain stem reticulospinal neurons, and calcitonin-gene–related peptide (CGRP) and neuropeptide Y (NPY), which are contained in primary afferents and sensory interneurons, respectively. Each of the peptides reduced the amplitude of monosynaptic reticulospinal-evoked excitatory postsynaptic potentials (EPSPs). The modulation appeared to be presynaptic, because postsynaptic input resistance and membrane potential, the amplitude of the electrical component of the EPSP, postsynaptic responses to glutamate, and spontaneous miniature EPSP amplitudes were unaffected. In addition, none of the peptides affected the pattern of N-methyl-d-aspartate (NMDA)–evoked locomotor activity in the isolated spinal cord. Potential interactions between the peptides were also examined. The “brain stem peptides” CCK and PYY had additive inhibitory effects on reticulospinal inputs, as did the “sensory peptides” CGRP and NPY. Brain stem peptides also had additive inhibitory effects when applied with sensory peptides. However, sensory peptides increased or failed to affect the amplitude of reticulospinal inputs in the presence of the brain stem peptides. These interactive effects also appear to be mediated presynaptically. The functional consequence of the peptidergic modulation was investigated by examining spinal ventral root responses elicited by brain stem stimulation. CCK and CGRP both reduced ventral root responses, although in interaction both increased the response. These results thus suggest that neuropeptides presynaptically influence the descending activation of spinal locomotor networks, and that they can have additive or novel interactive effects depending on the peptides examined and the order of their application.

Activation of pharmacologically distinct metabotropic glutamate receptors depresses reticulospinal-evoked monosynaptic EPSPs in the lamprey spinal cord

1996 ◽  
Vol 76 (6) ◽  
pp. 3834-3841 ◽  
Author(s):  
P. Krieger ◽  
A. el Manira ◽  
S. Grillner
Keyword(s):  
Spinal Cord ◽  
Synaptic Transmission ◽  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Input Resistance ◽  
Spinal Neurons ◽  
Metabotropic Glutamate ◽  
Apparent Change ◽  
Glutamatergic Synaptic Transmission ◽  
Presynaptic Mechanisms

1. Different metabotropic glutamate receptors (mGluRs) can modulate synaptic transmission in different regions in the CNS, but their roles at individual synaptic connections have not been detailed. We used paired intracellular recordings from reticulospinal axons and their postsynaptic target neurons in the lamprey spinal cord to investigate the effects of mGluR activation on glutamatergic synaptic transmission. 2. The mGluR agonists (1S,3R)-1-aminocyclopentane-1,3-dicarboxyylic acid [(1S,3R)-ACPD] and L(+)-2-amino-4-phosphonobutyric acid (L-AP4) both reduced the amplitude of monosynaptic excitatory postsynaptic potentials (EPSPs) elicited by stimulation of single reticulospinal axons. The depression of monosynaptic unitary EPSPs occurred without any apparent change in the input resistance of postsynaptic neurons. Furthermore, the mGluR agonists did not affect the amplitude of (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-induced depolarizations. Taken together, these results thus suggest that (1S,3R)-ACPD and L-AP4 depress reticulospinal synaptic transmission via presynaptic mechanisms. 3. (2S,1'S,2'S)-2-(carboxycyclopropyl) glycine (L-CCG-I), which selectively activates group II mGluRs, also reduced the amplitude of reticulospinal-evoked EPSPs without any apparent change in the input resistance or membrane potential of the postsynaptic neuron. 4. The mGluR antagonist alpha-methyl-L-AP4 blocked the depression induced by L-AP4 but not that induced by (1S,3R)-ACPD. Furthermore, the effects of coapplication of (1S,3R)-ACPD and L-AP4 were additive, suggesting that they inhibit synaptic transmission by an action on pharmacologically distinct mGluRs. 5. These results provide evidence for the colocalization of at least two different subtypes of presynaptic mGluRs on a single reticulospinal axon in the lamprey. These presynaptic mGluRs could serve as glutamatergic autoreceptors limiting the extent of reticulospinal-mediated excitation of spinal neurons.

scholarly journals The dopamine D1–D2DR complex in the rat spinal cord promotes neuropathic pain by increasing neuronal excitability after chronic constriction injury

2021 ◽  
Author(s):  
Yi-Ni Bao ◽  
Wen-Ling Dai ◽  
Ji-Fa Fan ◽  
Bin Ma ◽  
Shan-Shan Li ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Intracellular Calcium ◽  
Calcium Concentration ◽  
Neuronal Excitability ◽  
Chronic Constriction Injury ◽  
Pain Modulation ◽  
Intracellular Calcium Concentration ◽  
Rat Spinal Cord ◽  
Spinal Neurons

AbstractDopamine D1 receptor (D1DR) and D2 receptor (D2DR) are closely associated with pain modulation, but their exact effects on neuropathic pain and the underlying mechanisms remain to be identified. Our research revealed that intrathecal administration of D1DR and D2DR antagonists inhibited D1–D2DR complex formation and ameliorated mechanical and thermal hypersensitivity in chronic constriction injury (CCI) rats. The D1–D2DR complex was formed in the rat spinal cord, and the antinociceptive effects of D1DR and D2DR antagonists could be reversed by D1DR, D2DR, and D1–D2DR agonists. Gαq, PLC, and IP3 inhibitors also alleviated CCI-induced neuropathic pain. D1DR, D2DR, and D1–D2DR complex agonists all increased the intracellular calcium concentration in primary cultured spinal neurons, and this increase could be reversed by D1DR, D2DR antagonists and Gαq, IP3, PLC inhibitors. D1DR and D2DR antagonists significantly reduced the expression of p-PKC γ, p-CaMKII, p-CREB, and p-MAPKs. Levo-corydalmine (l-CDL), a monomeric compound in Corydalis yanhusuo W.T. Wang, was found to obviously suppress the formation of the spinal D1–D2DR complex to alleviate neuropathic pain in CCI rats and to decrease the intracellular calcium concentration in spinal neurons. l-CDL-induced inhibition of p-PKC γ, p-MAPKs, p-CREB, and p-CaMKII was also reversed by D1DR, D2DR, and D1–D2DR complex agonists. In conclusion, these results indicate that D1DR and D2DR form a complex and in turn couple with the Gαq protein to increase neuronal excitability via PKC γ, CaMKII, MAPK, and CREB signaling in the spinal cords of CCI rats; thus, they may serve as potential drug targets for neuropathic pain therapy.

Prostacyclin Regulates Spinal Nociceptive Processing through Cyclic Adenosine Monophosphate–induced Translocation of Glutamate Receptors

2014 ◽  
Vol 120 (2) ◽  
pp. 447-458 ◽  
Author(s):  
Claus Dieter Schuh ◽  
Christian Brenneis ◽  
Dong Dong Zhang ◽  
Carlo Angioni ◽  
Yannick Schreiber ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Prostaglandin E2 ◽  
Dorsal Horn ◽  
Central Sensitization ◽  
Glutamate Release ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Peripheral Inflammation ◽  
Wild Type ◽  
Spinal Neurons

Abstract Background: Prostacyclin (PGI2) is known to be an important mediator of peripheral pain sensation (nociception) whereas little is known about its role in central sensitization. Methods: The levels of the stable PGI2-metabolite 6-keto-prostaglandin F1α (6-keto-PGF1α) and of prostaglandin E2 (PGE2) were measured in the dorsal horn with the use of mass spectrometry after peripheral inflammation. Expression of the prostanoid receptors was determined by immunohistology. Effects of prostacyclin receptor (IP) activation on spinal neurons were investigated with biochemical assays (cyclic adenosine monophosphate-, glutamate release-measurement, Western blot analysis) in embryonic cultures and adult spinal cord. The specific IP antagonist Cay10441 was applied intrathecally after zymosan-induced mechanical hyperalgesia in vivo. Results: Peripheral inflammation caused a significant increase of the stable PGI2 metabolite 6-keto-PGF1α in the dorsal horn of wild-type mice (n = 5). IP was located on spinal neurons and did not colocalize with the prostaglandin E2 receptors EP2 or EP4. The selective IP-agonist cicaprost increased cyclic adenosine monophosphate synthesis in spinal cultures from wild-type but not from IP-deficient mice (n = 5–10). The combination of fluorescence-resonance–energy transfer–based cyclic adenosine monophosphate imaging and calcium imaging showed a cicaprost-induced cyclic adenosine monophosphate synthesis in spinal cord neurons (n = 5–6). Fittingly, IP activation increased glutamate release from acute spinal cord sections of adult mice (n = 13–58). Cicaprost, but not agonists for EP2 and EP4, induced protein kinase A–dependent phosphorylation of the GluR1 subunit and its translocation to the membrane. Accordingly, intrathecal administration of the IP receptor antagonist Cay10441 had an antinociceptive effect (n = 8–11). Conclusion: Spinal prostacyclin synthesis during early inflammation causes the recruitment of GluR1 receptors to membrane fractions, thereby augmenting the onset of central sensitization.

scholarly journals Cellular and Synaptic Actions of Acetylcholine in the Lamprey Spinal Cord

2008 ◽  
Vol 100 (2) ◽  
pp. 1020-1031 ◽  
Author(s):  
Katharina A. Quinlan ◽  
James T. Buchanan
Keyword(s):  
Spinal Cord ◽  
Input Resistance ◽  
Local Application ◽  
Spinal Motoneurons ◽  
Muscarinic Agonists ◽  
Spinal Neurons ◽  
Cholinergic Interneurons ◽  
Retrograde Filling ◽  
Feedback Pathway

This study investigated cellular and synaptic mechanisms of cholinergic neuromodulation in the in vitro lamprey spinal cord. Most spinal neurons tested responded to local application of acetylcholine (ACh) with depolarization and decreased input resistance. The depolarization persisted in the presence of either tetrodotoxin or muscarinic antagonist scopolamine and was abolished with nicotinic antagonist mecamylamine, indicating a direct depolarization through nicotinic ACh receptors. Local application of muscarinic ACh agonists modulated synaptic strength in the spinal cord by decreasing the amplitude of unitary excitatory and inhibitory postsynaptic potentials. The postsynaptic response to direct application of glutamate was unchanged by muscarinic agonists, suggesting a presynaptic mechanism. Cholinergic feedback from motoneurons was assessed using stimulation of a ventral root in the quiescent spinal cord while recording intracellularly from spinal motoneurons or interneurons. Mainly depolarizing potentials were observed, a portion of which was insensitive to removal of extracellular Ca2+, indicating electrotonic coupling. Hyperpolarizing potentials were also observed and were attenuated by the glycinergic antagonist strychnine, whereas depolarizing responses were potentiated by strychnine. Mecamylamine also reduced hyperpolarizing responses. The pharmacology of these responses suggests a Renshaw-like feedback pathway in lamprey. Immunohistochemistry for choline acetyltransferase, performed in combination with retrograde filling of motoneurons, demonstrated a population of nonmotoneuron cholinergic cells in the lamprey spinal cord. Thus endogenous cholinergic modulation of the lamprey spinal locomotor network is likely produced by both motoneurons and cholinergic interneurons acting via combined postsynaptic and presynaptic actions.

Neurotensin-induced modulation of spinal neurons and fictive locomotion in the lamprey

1995 ◽  
Vol 73 (3) ◽  
pp. 1308-1312 ◽  
Author(s):  
J. Y. Barthe ◽  
S. Grillner
Keyword(s):  
Spinal Cord ◽  
Grey Matter ◽  
Slow Phase ◽  
Cycle Duration ◽  
Fictive Locomotion ◽  
Intracellular Recordings ◽  
Spinal Neurons ◽  
Bath Application ◽  
Stretch Receptors ◽  
Consistent Change

1. Neurotensin containing interneurons are present in the spinal cord of both mammalian and nonmammalian vertebrates, but as yet little is known about their functional role. In this study we examine the effect of neurotensin on spinal cells and on the central pattern generator for locomotion in the lamprey spinal cord. 2. Bath application of neurotensin (10(-8) to 10(-6) M) slowed down the fictive locomotor activity induced by the glutamate agonist N-methyl-D-aspartate in the isolated spinal cord. The duration of the bursts of activity in the ventral roots increased in proportion to the increase of the locomotor cycle duration. 3. Intracellular recordings from grey matter neurons and intraspinal stretch receptors neurons showed that neurotensin induced a depolarization [4.4 +/- 0.5 (SE) mV, n = 19]. This depolarization could still be obtained after a blockade of voltage-sensitive sodium channels with tetrodotoxin (1.5 +/- 0.5 mV; n = 6), and after removal of calcium (2.8 +/- 0.4 mV; n = 5). Moreover no consistent change occurred in the fast and slow phase of the afterhyperpolarization (AHP) both of which are carried by potassium currents.

Clonidine-induced Neuronal Activation in the Spinal Cord Is Altered after Peripheral Nerve Injury

2003 ◽  
Vol 98 (3) ◽  
pp. 748-753 ◽  
Author(s):  
Carlo Pancaro ◽  
Weiya Ma ◽  
Michelle Vincler ◽  
Frederic Duflo ◽  
James C. Eisenach
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Nerve Injury ◽  
Mechanical Allodynia ◽  
Cholinergic Neurons ◽  
Camp Response Element Binding ◽  
Neuronal Activation ◽  
Cholinergic Interneurons ◽  
Intrathecal Clonidine ◽  
Number Of Cells

Background Alpha 2 adrenoceptor agonists produce antinociception in normal animals and alleviate mechanical allodynia in animals with nerve injury, although their mechanism of action may differ in these situations. The purpose of this study was to examine the location and number of cells in the spinal cord activated by intrathecal clonidine in these two circumstances and to test whether one class of interneurons, cholinergic, express alpha 2 adrenoceptors. Methods Intrathecal saline or clonidine, 10 and 30 microg, was injected in normal rats or those with mechanical allodynia following partial sciatic nerve section. Two hours later, animals were anesthetized and pericardially perfused. The number of cells in superficial and deep dorsal horn laminae at the L4-L5 level immunostained for phosphorylated cAMP response element binding protein (pCREB) were quantified. In separate studies, the authors colocalized alpha2C adrenoceptors with cholinergic neurons. Results Intrathecal clonidine increased pCREB immunoreactive cells in both superficial and deep laminae by 50-100% in normal animals. The number of pCREB immunoreactive cells increased in nerve-injured compared to normal rats. Intrathecal clonidine decreased pCREB immunoreactive cells in the deep dorsal horn of injured animals. Alpha2C adrenoceptors colocalized with cholinergic neurons in both superficial and deep dorsal horn. Discussion Previous studies suggest a shift in alpha 2 adrenoceptor subtype and the involvement of cholinergic interneurons in antinociception in the spinal cord after nerve injury. The current results suggest that intrathecal clonidine, by direct or indirect methods, increases neuronal activation in normal animals, presumably leading to net inhibition of pain signaling, whereas it reduces the increase in neuronal activity induced by nerve injury.

Riluzole decreases flexion withdrawal reflex but not voluntary ankle torque in human chronic spinal cord injury

2011 ◽  
Vol 105 (6) ◽  
pp. 2781-2790 ◽  
Author(s):  
Renée D. Theiss ◽  
T. George Hornby ◽  
W. Zev Rymer ◽  
Brian D. Schmit
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuronal Excitability ◽  
Spinal Neurons ◽  
Chronic Spinal Cord Injury ◽  
Persistent Inward Currents ◽  
Reflex Responses ◽  
Withdrawal Reflex ◽  
Cord Injury ◽  
Inward Currents

The objectives of this study were to probe the contribution of spinal neuron persistent sodium conductances to reflex hyperexcitability in human chronic spinal cord injury. The intrinsic excitability of spinal neurons provides a novel target for medical intervention. Studies in animal models have shown that persistent inward currents, such as persistent sodium currents, profoundly influence neuronal excitability, and recovery of persistent inward currents in spinal neurons of animals with spinal cord injury routinely coincides with the appearance of spastic reflexes. Pharmacologically, this neuronal excitability can be decreased by agents that reduce persistent inward currents, such as the selective persistent sodium current inhibitor riluzole. We were able to recruit seven subjects with chronic incomplete spinal cord injury who were not concurrently taking antispasticity medications into the study. Reflex responses (flexion withdrawal and H-reflexes) and volitional strength (isometric maximum voluntary contractions) were tested at the ankle before and after placebo-controlled, double-blinded oral administration of riluzole (50 mg). Riluzole significantly decreased the peak ankle dorsiflexion torque component of the flexion withdrawal reflex. Peak maximum voluntary torque in both dorsiflexion and plantarflexion directions was not significantly changed. Average dorsiflexion torque sustained during the 5-s isometric maximum voluntary contraction, however, increased significantly. There was no effect, however, on the monosynaptic plantar and dorsiflexor H-reflex responses. Overall, these results demonstrate a contribution of persistent sodium conductances to polysynaptic reflex excitability in human chronic spinal cord injury without a significant role in maximum strength production. These results suggest that intrinsic spinal cellular excitability could be a target for managing chronic spinal cord injury hyperreflexia impairments without causing a significant loss in volitional strength.

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