Skip to main content
SpringerLink
Log in
Book cover

Molecular Pain pp 295–307Cite as

Silent Glutamatergic Synapses and Long-term Facilitation in Spinal Dorsal Horn Neurons

  • Chapter

Abstract

Neurons in the superficial dorsal horn of the spinal cord are important for conveying sensory information from the periphery to the central nervous system. It has been proposed that some synapses between primary afferent fibers and spinal dorsal horn neurons are inefficient or silent. Ineffective sensory transmission could result from a small postsynaptic current that fails to depolarize the cell to threshold for an action potential or a cell with a normal postsynaptic current but an increased threshold for action potentials. One possible mechanism for ineffective synapses is the existent of silent glutamatergic synapses. In silent synapses, postsynaptic dorsal horn neurons lack functional AMPA/KA receptors and no synaptic responses are detected even when glutamate is released from presynaptic sensory afferent fibers. Serotonin (5-HT), a major neurotransmitter of the raphe-spinal projecting pathway, transforms silent glutamatergic synapses into functional ones by recruiting postsynaptic functional AMPA receptors. AMPA receptor interaction with PDZ-containing proteins is critical for 5-HT induced recruitment. Silent synapses, as well as their recruitment mechanisms, are developmentally regulated and can still be found in adult synapses. However, they are “functional” and contribute to some sensory transmission. The recruitment of AMPA receptors into pure NMDA receptor containing sensory synapses requires coactivation of 5-HT and postsynaptic adenylyl cyclases. The recruitment of silent glutamatergic synapses provides a synaptic mechanism for spinal senstization in pathological pain, including possible pheonotype switching of dorsal horn neurons. These results suggest that the transformation of silent glutamatergic synapses may serve as a cellular mechanism for central plasticity in the spinal cord.

The introduction of Dr. Zhuo, please refer to Chapter 8.

This is a preview of subscription content, log in via an institution.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

General Citations

  • Bliss TVP and Collingridge GL. 1993. A synaptic model of memory: long-term potentiation in the hippocampus. Nature, 361: 31–39.

    Article  PubMed  CAS  Google Scholar 

  • Fields HL, Heinricher MM and Mason P. 1991 Neurotransmitters in nociceptive modulatory circuits. Annu Rev Neurosci, 14: 219–245.

    Article  PubMed  CAS  Google Scholar 

  • Garner CC, Nash J and Huganir RL. 2000. PDZ domains in synapse assembly and signaling. Trends Cell Biol, 10: 274–280.

    Article  PubMed  CAS  Google Scholar 

  • Hollmann M and Heinemann S. 1994. Cloned glutamate receptors. Annu Rev Neurosci, 17: 31–108.

    Article  PubMed  CAS  Google Scholar 

  • Lisman J. 1989. A mechanism for the Hebb and the anti-Hebb processes underlying learning and memory. Proc Natl Acad Sci USA, 86: 9574–9578.

    Article  PubMed  CAS  Google Scholar 

  • Zhuo M. 2000. Silent glutamatergic synapses and long-term facilitation in spinal dorsal horn neurons. Prog Brain Res, 129:101–113.

    Article  PubMed  CAS  Google Scholar 

  • Zhuo M. 2002. Glutamate receptors and persistent pain: targeting forebrain NR2B subunits. Drug Discov Today, 7:259–267.

    Article  PubMed  CAS  Google Scholar 

  • Zhuo M. 2004. Central plasticity in pathological pain. The Novaris Foundation Symposium, Pathological pain: from molecular to clinical aspects. Chichester: Wiley. 132–148.

    Chapter  Google Scholar 

Discovery Citations

  • Baba H, Doubell TP, Moore KA and Woolf CJ. 2000. Silent NMDA receptor-mediated synapses are developmentally regulated in the dorsal horn the rat spinal cord. J Neurophysiol, 83: 955–962.

    PubMed  CAS  Google Scholar 

  • Bardoni R, Magherini PC and MacDermott AB. 1998. NMDA EPSCs at glutamatergic synapses in the spinal cord dorsal horn of the postnatal rat. J Neurosci, 18: 6558–6567.

    PubMed  CAS  Google Scholar 

  • Bardoni R, Magherini PC and MacDermott AB. 2000. Activation of NMDA receptors drives action potentials in superficial dorsal horn from neonatal rats. NeuroReport, 11:1721–1727.

    Article  PubMed  CAS  Google Scholar 

  • Bowker RM and Abbott LC. 1990. Quantitative re-evaluation of descending serotonergic and non-serotonergic projections from the medulla of the rodent: evidence for extensive co-existence of serotonin and peptides in the same spinally projecting neurons, but not from the nucleus raphe magnus. Brain Res, 512:15–25.

    Article  PubMed  CAS  Google Scholar 

  • Cerne R, Jinag M and Randic M. 1992. Cyclic adenosine 3′,5′-monophosphate potentiates excitatory amino acid synaptic responses of rat spinal dorsal horn neurons. Brain Res, 596:111–123.

    Article  PubMed  CAS  Google Scholar 

  • Chavez-Noriega LE and Stevens CF. 1992. Modulation of synaptic efficacy in field CA1 of the rat hippocampus by forskolin. Brain Res, 574:85–92.

    Article  PubMed  CAS  Google Scholar 

  • Durand GM, Kovalchuk Y and Konnerth A. 1996. Long-term potentiation and functional synapse induction in developing hippocampus. Nature, 381: 71–75.

    Article  PubMed  CAS  Google Scholar 

  • Gil Z and Amitai Y. 1996. Adult thalamocortical transmission involves both NMDA and non-NMDA receptors. J Neurophysiol, 76:2547–2554.

    PubMed  CAS  Google Scholar 

  • Gomperts SN, Rao A, Craig AM, Malenka RC and Nicoll RA. 1998. Postsynaptically silent synapses in signle neuron cultures. Neuron, 21:1443–1451.

    Article  PubMed  CAS  Google Scholar 

  • Gu JG, Albuquerque C, Lee CJ and MacDermott AB. 1996. Synaptic strengthing through activation of Ca2+-permeable AMPA receptors. Nature, 381: 793–796.

    Article  PubMed  CAS  Google Scholar 

  • Haber LH, Martin RF, Chung JM and Willis WD. 1990. Inhibition and excitation of primate spinothalamic tract neurons by stimulation in region of nucleus reticularis gigantocellularis. J Neurophysiol, 43:1578–1593.

    Google Scholar 

  • Hayashi Y, Shi SH, Esteban JA, Piccini A, Poncer JC and Malinow R. 2000. Driving AMPA receptors into synapses by LTP and CaMKII: requirement for GluRl and PDZ domain interaction. Science, 287:2262–2267.

    Article  PubMed  CAS  Google Scholar 

  • Hori Y, Endo K and Takahashi T. 1996. Long-lasting synaptic facilitation induced by serotonin in superficial dorsal horn neurones of the rat spinal cord. J Physiol (Lond), 492: 867–876.

    CAS  Google Scholar 

  • Isaac JTR, Crair MC, Nicoll RA and Malenka RC. 1997. Silatit synapses during development of thalamocortical inputs. Neuron, 18: 269–280.

    Article  PubMed  CAS  Google Scholar 

  • Isaac JTR, Nicoll RA and Malenka RC. 1995. Evidence for silent synapses: implications for the expression of LTP. Neuron, 15: 427–434.

    Article  PubMed  CAS  Google Scholar 

  • Lee HK, Barbarosie M, Kameyama K, Bear MF and Huganir RL. 2000. Regulation of distinct AMPA receptor phosphrylation sites during bi-directional synaptic plasticity. Nature, 405:955–959.

    Article  PubMed  CAS  Google Scholar 

  • Li P and Zhuo M. 1998. Silent glutamatergic synapses and nociception in mammalian spinal cord. Nature, 393: 695–698.

    Article  PubMed  CAS  Google Scholar 

  • Li P and Zhuo M. 2001. Cholinergic, noradrenergic, and serotonergic inhibition of fast synaptic transmission in spinal lumbar dorsal horn of rat. Brain Res Bull, 54:639–647.

    Article  PubMed  CAS  Google Scholar 

  • Li P, Kerchner GA, Sala C, Wei F, Huettner JE, Sheng M and Zhuo M. 1999. AMPA receptor-PDZ interactions in facilitation of spinal sensory synapses. Nature Neurosci, 2:972–977.

    Article  PubMed  CAS  Google Scholar 

  • Liao D, Hessler NA and Malinow R. 1995. Activation of post-synaptically silent synapses during pairing-induced LTP in CA1 region of hippocampal slice. Nature, 375: 400–404.

    Article  PubMed  CAS  Google Scholar 

  • Liao D, Zhang X, O’Brien R, Ehlers M and Hugnir RL. 1999. Regulation of morphological postsynaptic silent synapses in developing hippocampal neurons. Nature Neurosci, 2:37–43.

    Article  PubMed  CAS  Google Scholar 

  • Light AR, Trevino DL and Perl ER. 1979. Morphological features of functionally defined neurons in the marginal zone and substantia gelatinosa of the spinal dorsal horn. J Comp Neurol, 186:151–171.

    Article  PubMed  CAS  Google Scholar 

  • Light AR, Casale EJ and Menetrey DM. 1986. The effects of focal stimulation in nucleus raphe magnus and periaqueductal gray on intracellularly recorded neurons in spinal laminae I and II. J Neurophysiol, 56:555–571.

    PubMed  CAS  Google Scholar 

  • Lopez-Garcia JA and King AE. 1996. Pre-and post-synaptic actions of 5-hydroxytryptamine in the rat lumbar dorsal horn in vitro: implications for somatosensory transmission. Eur J Neurosci, 8: 2188–2197.

    Article  PubMed  CAS  Google Scholar 

  • Malenka RC and Nicoll RA. 1997. Silent synapses speak up. Neuron, 19:473–476.

    Article  PubMed  CAS  Google Scholar 

  • Malenka RC and Nicoll RA. 2000. Long-term potentiation—a decade of progress? Science, 285: 1870–1874.

    Article  Google Scholar 

  • Malinow R, Mainen ZF and Hayashi Y. 2000. LTP mechanisms: from silence to four-lane traffic. Curr Opin Neurobiol, 10:352–357.

    Article  PubMed  CAS  Google Scholar 

  • McCreery DB, Bloedel JR and Hames EG. 1979. Effects of stimulating in raphe nuclei and in reticular formation on response of spinothalamic neurons to mechanical stimuli. J Neurophysiol, 42:166–182.

    PubMed  CAS  Google Scholar 

  • Petralia RS, Estban JA, Wang YX, Partridge JG, Zhao HM, Wenthold RJ and Malinow R. 1999. Selective acquisition of AMPA receptors over postnatal development suggests a molecular basis for silent synapses. Nature Neurosci, 2: 31–36.

    Article  PubMed  CAS  Google Scholar 

  • Rumpel S, Hart H and Gottmann K. 1998. Silent synapses in the developing rat visual cortex: evidence for postsynaptic expression of synaptic plasticity. J Neurosci, 18: 8863–8874.

    PubMed  CAS  Google Scholar 

  • Sah P, Hestrin S and Nicoll RA. 1989. Tonic activation of NMDA receptors by ambient glutamate enhances excitability of neurons. Science, 246: 815–818.

    Article  PubMed  CAS  Google Scholar 

  • Schiller J, Major G, Koester HJ and Schiller Y. 2000. NMDA spikes in basal dendrites of cortical pyramidal neurons. Nature, 404:285–289.

    Article  PubMed  CAS  Google Scholar 

  • Schoppa NE, Kinzie JM, Sahara Y, Segerson TP and Westbrook GL. 1998. Dendrodendritic inhibition in the olfactory bulb is driven by NMDA receptors. J Neurosci, 8:6790–6802.

    Google Scholar 

  • Seeburg PH. 1993. The molecular biology of mammalian glutamate receptor channels. Trends Neurosci, 16: 359–365.

    Article  PubMed  CAS  Google Scholar 

  • Solomon RE and Gebhart GF. 1988. Mechanisms of effects of intrathecal serotonin on nociception and blood pressure in rats. J Pharmacol Exp Ther, 245:905–912.

    PubMed  CAS  Google Scholar 

  • Sorkin LS, McAdoo DJ and Willis WD. 1993. Raphe magnus stimulation-induced antinociception in the cat is associated with release of amino acids as well as serotonin in the lumbar dorsal horn. Brain Res, 618:95–108.

    Article  PubMed  CAS  Google Scholar 

  • Tan HJ and Miletic V. 1990. Electrophysiological properties of frog spinal dorsal horn neurons and their responses to serotonin: an intracellular study in the isolated hemisected spinal cord. Brain Res, 528:344–348.

    Article  PubMed  CAS  Google Scholar 

  • Wall PD. 1977. The presence of ineffective synapses and the circumstances which unmask them. Phil Trans R Soc Lond. B., 278: 361–372.

    Article  CAS  Google Scholar 

  • Wall PD. 1988. Recruitment of ineffective synapses after injury. In: Advances in Neurology. Vol. 47. Waxman SG, ed. New York: Raven Press. 387–400.

    Google Scholar 

  • Weisskopf MG, Castillo PE, Zalutsky RA and Nicoll RA. 1994. Mediation of hippocampal mossy fiber longterm potentiation by cyclic AMP. Science, 265:1878–1882.

    Article  PubMed  CAS  Google Scholar 

  • Willis WD. 1982. Control of nociceptive transmission in the spinal cord. In: Progress in Sensory Physiology. Vol. 3. Ottoson D, ed. Berlin: Springer-Verlag. 1–159.

    Google Scholar 

  • Wu GY, Malinow R and Cline HT. 1996. Maturation of a central glutamatergic synapse. Science, 274: 972–976.

    Article  PubMed  CAS  Google Scholar 

  • Xia Z and Storm DR. 1997. Calmodulin-regulated adenylyl cyclases and neuromodulation. Current Opinion in Neurobiology, 7: 391–396.

    Article  PubMed  CAS  Google Scholar 

  • Yoshimura M and Jessell TM. 1989. Primary afferent-evoked synaptic responses and slow potential generation in rat substantia gelitinosa neurons in vitro. J Neurophysiol, 62: 96–108.

    PubMed  CAS  Google Scholar 

  • Yoshimura M and Jessell TM. 1990. Amino acid-mediated EPSPs at primary afferent synapses with substantia gelatinosa neurones in the rat spinal cord. J Physiol (Lond), 430:315–335.

    CAS  Google Scholar 

  • Zemlan FP, Kow LM and Pfaff DW. 1983. Spinal serotonin (5-HT) receptor subtypes and nociception. J Pharmacol Exp Ther, 226:477–485.

    PubMed  CAS  Google Scholar 

  • Zhuo M and Gebhart GF. 1990. Characterization of descending inhibition and facilitation from the nuclei reticularis gigantocellularis and gigantocellularis pars alpha in the rat. Pain, 42:337–350.

    Article  PubMed  CAS  Google Scholar 

  • Zhuo M and Gebhart GF. 1991. Spinal serotonin receptors mediate descending inhibition and facilitation from the nuclei reticularis gigantocellularis and gigantocellularis pars alpha in the rat. Brain Res, 550:35–48.

    Article  PubMed  CAS  Google Scholar 

  • Zhuo M and Gebhart GF. 1992. Characterization of descending facilitation and inhibition of spinal nociceptive transmission from the nuclei reticularis gigantocellularis and gigantocellularis pars alpha in the rat. J Neurophysiol, 67:1599–1614.

    PubMed  CAS  Google Scholar 

  • Zhuo M and Gebhart GF. 1997. Biphasic modulation of spinal nociceptive transmission from the medullary raphe nuclei in the rat. J Neurophysiol, 78: 746–758.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology, University of Toronto, Medical Sciences Bldg, Rm 3342, 1 King’s College Circle, Toronto, Ontario, M5S 1A8, Canada

    Min Zhuo PhD (Canada Research Chair in Pain and Cognition, Tier I EJLB-CIHR Michael Smith Chair in Neurosciences and Mental Health and Professor)

Authors
  1. Min Zhuo PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Physiology, University of Toronto, Medical Sciences Bldg, Rm 3342 1 King’s College Circle, Toronto, Ontario, Canada, M5S 1A8

    Min Zhuo

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Higher Education Press

About this chapter

Cite this chapter

Zhuo, M. (2007). Silent Glutamatergic Synapses and Long-term Facilitation in Spinal Dorsal Horn Neurons. In: Zhuo, M. (eds) Molecular Pain. Springer, New York, NY. https://doi.org/10.1007/978-0-387-75269-3_22

Download citation

  • DOI: https://doi.org/10.1007/978-0-387-75269-3_22

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-0-387-75268-6

  • Online ISBN: 978-0-387-75269-3

Publish with us

Policies and ethics

Search

Navigation