Serotonin1A facilitation of frog motoneuron responses to afferent stimuli and toN-methyl-d-aspartate

Holohean, Alice M.; Hackman, J.C.; Shope, S.B.; Davidoff, Robert A.

doi:10.1016/0306-4522(92)90506-w

Cited by 21 publications

(12 citation statements)

References 37 publications

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“…NMDA channels and 5HT receptors are integral in the regulation of spinal reflexes and rhythmic motor pathways (13,14,(75)(76)(77). Activation of 5HT2C receptors induces long lasting reflexes (78), and after spinal cord injury, locomotion in rats requires constitutive activity of 5HT2C receptors (79).…”

Section: Discussionmentioning

confidence: 99%

“…There are 7 classes of 5HT receptors with 1, 2, and 4 -7 classes that are generally considered to be G-proteincoupled receptors; the exception, 5HT3, forms an ion channel. NMDA-mediated motoneuronal activity has been shown to be depressed by the activation of 5HT2A and facilitated by 5HT1A and 5HT2B receptor subtypes (12)(13)(14)(15). The role of NMDA sub-units in 5HT-mediated modulation of NMDA-induced motoneuronal depolarization has not been explored.…”

Section: Nmdamentioning

confidence: 99%

“…Serotonin (5-hydroxytryptamine; 5HT) is a major neuromodulator of NMDA-mediated motoneuron output (12)(13)(14)(15). Spinal motoneurons express a variety of 5HT receptor subtypes (16 -20) that are activated by 5HT released from tracts descending from the raphe nuclei (21) and also by 5HT circulating extrasynaptically (22).…”

Section: Nmdamentioning

confidence: 99%

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5-Hydroxytryptamine 5HT2C Receptors Form a Protein Complex with N-Methyl-d-aspartate GluN2A Subunits and Activate Phosphorylation of Src Protein to Modulate Motoneuronal Depolarization

Bigford

Chaudhry

Keane

et al. 2012

Journal of Biological Chemistry

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Background: 5-Hydroxytryptamine (5HT) modulates N-methyl-D-aspartate (NMDA) depolarization. Results: 5HT2C co-immunoprecipitates with GluN2A and enhances NMDA motoneuronal depolarization through phosphorylation of Src . Conclusion: 5HT modulates NMDA through Src phosphorylation in a molecular complex that is localized in the processes of spinal neurons. Significance: 5HT2C modulation of NMDA excitation is coordinated by a molecular complex.

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Section: Discussionmentioning

confidence: 99%

Section: Nmdamentioning

confidence: 99%

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5-Hydroxytryptamine 5HT2C Receptors Form a Protein Complex with N-Methyl-d-aspartate GluN2A Subunits and Activate Phosphorylation of Src Protein to Modulate Motoneuronal Depolarization

Bigford

Chaudhry

Keane

et al. 2012

Journal of Biological Chemistry

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“…5-HT 1A receptors have been described previously in amphibian spinal cord (Holohean et al, 1992;Tan and Miletic, 1992). The 5-HT 1A receptor can inhibit Ca 2ϩ entry through HVA channels into afferent terminals of nociceptors in mammalian spinal cord (Del Mar et al, 1994).…”

Section: Identity Of Serotonergic Receptorsmentioning

confidence: 99%

Serotonergic Inhibition of the T-Type and High Voltage-Activated Ca²⁺Currents in the Primary Sensory Neurons ofXenopusLarvae

Sun

Dale

1997

J. Neurosci.

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The primary sensory Rohon-Beard (R-B) neurons of Xenopus larvae are highly analogous to the C fibers of the mammalian pain pathway. We explored the actions of 5-HT by studying the modulation of Ca 2ϩ currents. In ϳ80% of the acutely isolated R-B neurons, 5-HT inhibited the high voltage-activated (HVA) currents by 16% (n ϭ 29) and the T-type currents by 24% (n ϭ 41). The modulation of the T-type and the HVA currents was mimicked by selective 5-HT 1A and 5-HT 1D agonists: 8-OH-DPAT and L-694,247. The effects of the agonists were blocked by their respective 5-HT 1A or 5-HT 1D antagonists: p-MPPI and GR127935, suggesting that both 5-HT 1A and 5-HT 1D receptors were involved. Approximately 70% of the actions of 5-HT on HVA currents was occluded by -conotoxin-GVIA (N-type channel blocker), whereas the rest of the modulation (ϳ30%) was occluded by Ͻ100 nM -agatoxin-TK (P/Q-type channel blocker). This suggests that 5-HT acts on N-and P/Q-type Ca 2ϩ channels. Neither the modulation of the T-type nor that of the HVA currents was accompanied by changes in their voltage-dependent kinetics. Cell-attached patch-clamp recordings suggest that the modulation of the T-type channel occurs through a membrane-delimited second messenger. We have studied the functional consequences of the modulation of T-type Ca 2ϩ channels and have found that these channels play a role in spike initiation in R-B neurons. Modulation of T-type channels by 5-HT therefore could modulate the sensitivity of this sensory pathway by increasing the thresholds of R-B neurons. This is a new and potentially important locus for modulation of sensory pathways in vertebrates.

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“…5-HT (25-50 iM) has been reported occasionally to enhance glutamate-induced depolarization in immature rat motoneurones (Wu et al, 1991). In (Holohean et al, 1992a), high concentrations of 5-HT (> 10 giM) reduced both synaptic 1 Author for correspondence. 2Present address: UPR 9011, Neurobiologie et Mouvements,31 ventral root potentials and postsynaptic responses to NMDA and kainate in the presence of TTX (Holohean et al, 1992b).…”

Section: Introductionmentioning

confidence: 99%

Voltage‐dependent block of NMDA responses by 5‐HT agonists in ventral spinal cord neurones

Chesnoy-Marchais

Barthe

1996

British J Pharmacology

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1 Modulation by 5-hydroxytryptamine receptor agonists of the NMDA responses of ventral spinal cord neurones was studied by use of the whole-cell patch-clamp technique. 2 In a Mg-free solution containing tetrodotoxin and glycine, 5-hydroxytryptamine (5-HT, 10-100 ,UM) reduced the NMDA response, the block increasing with hyperpolarization. Kainate responses were little affected. 3 Some classical agonists of 5-HT receptors induced similar blocking effects. At 10 IM, both a selective agonist of 5-HT2 receptors, (±)-2,5-dimethoxy-4 iodo amphetamine (DOI), and a selective agonist of some 5-HTI receptors, (±)-8-hydroxy-2(n-dipropyl amino) tetralin (8-OH-DPAT), induced pronounced blocking effects, of 48% and 33% respectively at -100 mV, whereas another 5-HT1 agonist, 5-carboxamidotryptamine (5-CT) was ineffective. At 100 gIM, 5-methoxytryptamine (5-MeOT) induced a complete block of the NMDA responses recorded at -100 mV. The order of potency was: 5-MeOT DOI> 8-OH-DPAT > 5-HT > 5-CT. 4 Neither spiperone nor ketanserin (1 riM) prevented the blocking effect of 5-HT or DOI. 5 Prolonged preincubations with 5-HT did not block the response if NMDA was applied without 5-HT. When 5-HT agonists were applied both by preincubation and with NMDA, the degree of block increased during the NMDA application.6 Lowering the NMDA concentration (from 100 to 20 giM) slightly decreased the blocking effect of 5-MeOT. 7 External Mg2+ ions (1 mM) also reduced the blocking effects of 5-HT and 5-MeOT. 8 The blocking effects described appear to be independent of classical 5-HT receptors. Their voltagedependence suggests a mechanism of open channel block consistent with all the results obtained.

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Serotonin1A facilitation of frog motoneuron responses to afferent stimuli and toN-methyl-d-aspartate

Cited by 21 publications

References 37 publications

5-Hydroxytryptamine 5HT2C Receptors Form a Protein Complex with N-Methyl-d-aspartate GluN2A Subunits and Activate Phosphorylation of Src Protein to Modulate Motoneuronal Depolarization

5-Hydroxytryptamine 5HT2C Receptors Form a Protein Complex with N-Methyl-d-aspartate GluN2A Subunits and Activate Phosphorylation of Src Protein to Modulate Motoneuronal Depolarization

Serotonergic Inhibition of the T-Type and High Voltage-Activated Ca²⁺Currents in the Primary Sensory Neurons ofXenopusLarvae

Voltage‐dependent block of NMDA responses by 5‐HT agonists in ventral spinal cord neurones

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Serotonin1A facilitation of frog motoneuron responses to afferent stimuli and toN-methyl-d-aspartate

Cited by 21 publications

References 37 publications

5-Hydroxytryptamine 5HT2C Receptors Form a Protein Complex with N-Methyl-d-aspartate GluN2A Subunits and Activate Phosphorylation of Src Protein to Modulate Motoneuronal Depolarization

5-Hydroxytryptamine 5HT2C Receptors Form a Protein Complex with N-Methyl-d-aspartate GluN2A Subunits and Activate Phosphorylation of Src Protein to Modulate Motoneuronal Depolarization

Serotonergic Inhibition of the T-Type and High Voltage-Activated Ca2+Currents in the Primary Sensory Neurons ofXenopusLarvae

Voltage‐dependent block of NMDA responses by 5‐HT agonists in ventral spinal cord neurones

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Serotonergic Inhibition of the T-Type and High Voltage-Activated Ca²⁺Currents in the Primary Sensory Neurons ofXenopusLarvae