Structural plasticity of axon initial segment in spinal cord neurons underlies inflammatory pain.
Journal
Pain
ISSN: 1872-6623
Titre abrégé: Pain
Pays: United States
ID NLM: 7508686
Informations de publication
Date de publication:
01 06 2023
01 06 2023
Historique:
received:
03
08
2022
accepted:
19
10
2022
medline:
15
5
2023
pubmed:
17
1
2023
entrez:
16
1
2023
Statut:
ppublish
Résumé
Physiological or pathology-mediated changes in neuronal activity trigger structural plasticity of the action potential generation site-the axon initial segment (AIS). These changes affect intrinsic neuronal excitability, thus tuning neuronal and overall network output. Using behavioral, immunohistochemical, electrophysiological, and computational approaches, we characterized inflammation-related AIS plasticity in rat's superficial (lamina II) spinal cord dorsal horn (SDH) neurons and established how AIS plasticity regulates the activity of SDH neurons, thus contributing to pain hypersensitivity. We show that in naive conditions, AIS in SDH inhibitory neurons is located closer to the soma than in excitatory neurons. Shortly after inducing inflammation, when the inflammatory hyperalgesia is at its peak, AIS in inhibitory neurons is shifted distally away from the soma. The shift in AIS location is accompanied by the decrease in excitability of SDH inhibitory neurons. These AIS location and excitability changes are selective for inhibitory neurons and reversible. We show that AIS shift back close to the soma, and SDH inhibitory neurons' excitability increases to baseline levels following recovery from inflammatory hyperalgesia. The computational model of SDH inhibitory neurons predicts that the distal shift of AIS is sufficient to decrease the intrinsic excitability of these neurons. Our results provide evidence of inflammatory pain-mediated AIS plasticity in the central nervous system, which differentially affects the excitability of inhibitory SDH neurons and contributes to inflammatory hyperalgesia.
Identifiants
pubmed: 36645177
doi: 10.1097/j.pain.0000000000002829
pii: 00006396-202306000-00018
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1388-1401Informations de copyright
Copyright © 2023 International Association for the Study of Pain.
Références
Baba H, Doubell TP, Woolf CJ. Peripheral inflammation facilitates Aβ fiber-mediated synaptic input to the substantia gelatinosa of the adult rat spinal cord. J Neurosci 1999;19:859–67.
Balasubramanyan S, Stemkowski PL, Stebbing MJ, Smith PA. Sciatic chronic constriction injury produces cell-type-specific changes in the electrophysiological properties of rat substantia gelatinosa neurons. J Neurophysiol 2006;96:579–90.
Baranauskas G, David Y, Fleidervish IA. Spatial mismatch between the Na+ flux and spike initiation in axon initial segment. Proc Natl Acad Sci U S A 2013;110:4051–6.
Barkai O, Butterman R, Katz B, Lev S, Binshtok AM. The input-output relation of primary nociceptive neurons is determined by the morphology of the peripheral nociceptive terminals. J Neurosci 2020;40:9346–63.
Barkai O, Puig S, Lev S, Title B, Katz B, Eli-Berchoer L, Gutstein HB, Binshtok AM. Platelet-derived growth factor activates nociceptive neurons by inhibiting M-current and contributes to inflammatory pain. PAIN 2019;160:1281–96.
Basbaum AI, Bautista DM, Scherrer GG, Julius D. Cellular and molecular mechanisms of pain. Cell 2009;139:267–84.
Battefeld A, Tran BT, Gavrilis J, Cooper EC, Kole MHP. Heteromeric Kv7.2/7.3 channels differentially regulate action potential initiation and conduction in neocortical myelinated axons. J Neurosci 2014;34:3719–32.
Bean BP. The action potential in mammalian central neurons. Nat Rev Neurosci 2007;8:451–65.
Bender KJ, Trussell LO. The physiology of the axon initial segment. Annu Rev Neurosci 2012;35:249–65.
Binshtok AM, Wang H, Zimmermann K, Amaya F, Vardeh D, Shi L, Brenner GJ, Ji R-RR, Bean BP, Woolf CJ, Samad TA. Nociceptors are interleukin-1 sensors. J Neurosci 2008;28:14062–73.
Braz J, Solorzano C, Wang X, Basbaum AI. Transmitting pain and itch messages: a contemporary view of the spinal cord circuits that generate gate control. Neuron 2014;82:1407–536.
Buffington SA, Rasband MN. The axon initial segment in nervous system disease and injury. Eur J Neurosci 2011;34:1609–19.
Chand AN, Galliano E, Chesters RA, Grubb MS. A distinct subtype of dopaminergic interneuron displays inverted structural plasticity at the axon initial segment. J Neurosci 2015;35:1573–90.
Coull JAM, Beggs S, Boudreau D, Boivin D, Tsuda M, Inoue K, Gravel C, Salter MW, de Koninck Y. BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 2005;438:1017–21.
Coull JAM, Boudreau D, Bachand K, Prescott SA, Nault F, Sík A, Koninck PD, Koninck YD. Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain. Nature 2003;424:938–42.
Devor M. Sodium channels and mechanisms of neuropathic pain. J Pain 2006;7:S3–S12.
Djouhri L, Koutsikou S, Fang X, McMullan S, Lawson SN. Spontaneous pain, both neuropathic and inflammatory, is related to frequency of spontaneous firing in intact C-fiber nociceptors. J Neurosci 2006;26:1281–92.
Dodge FA, Cooley JW. Action potential of the motorneuron. IBM J Res Develop 1973;17:219–29.
Dura-Bernal S, Suter BA, Gleeson P, Cantarelli M, Quintana A, Rodriguez F, Kedziora DJ, Chadderdon GL, Kerr CC, Neymotin SA, McDougal RA, Hines M, Shepherd GM, Lytton WW. NetPyNE, a tool for data-driven multiscale modeling of brain circuits. Elife 2019;8:e44494.
Evans MD, Sammons RP, Lebron S, Dumitrescu AS, Watkins TBK, Uebele VN, Renger JJ, Grubb MS. Calcineurin signaling mediates activity-dependent relocation of the axon initial segment. J Neurosci 2013;33:6950–63.
Eyal G, Mansvelder HD, de Kock CPJ, Segev I. Dendrites impact the encoding capabilities of the axon. J Neurosci 2014;34:8063–71.
Fékété A, Ankri N, Brette R, Debanne D. Neural excitability increases with axonal resistance between soma and axon initial segment. Proc Natl Acad Sci U S A 2021;118:e2102217118.
Galliano E, Hahn C, Browne LP, R Villamayor P, Tufo C, Crespo A, Grubb MS. Brief sensory deprivation triggers cell type-specific structural and functional plasticity in olfactory bulb neurons. J Neurosci 2021;41:2135–51.
Goethals S, Brette R. Theoretical relation between axon initial segment geometry and excitability. Elife 2020;9:e53432.
Goldstein RH, Barkai O, Íñigo-Portugués A, Katz B, Lev S, Binshtok AM. Location and plasticity of the sodium spike initiation zone in nociceptive terminals in vivo. Neuron 2019;102:801–12.e5.
Grubb MS, Burrone J. Activity-dependent relocation of the axon initial segment fine-tunes neuronal excitability. Nature 2010;465:1070–4.
Grubb MS, Shu Y, Kuba H, Rasband MN, Wimmer VC, Bender KJ. Short- and long-term plasticity at the axon initial segment. J Neurosci 2011;31:16049–55.
Gudes S, Barkai O, Caspi Y, Katz B, Lev S, Binshtok AM. The role of slow and persistent TTX-resistant sodium currents in acute tumor necrosis factor-alpha-mediated increase in nociceptors excitability. J Neurophysiol 2015;113:601–19.
Gulledge AT, Bravo JJ. Neuron morphology influences axon initial segment plasticity. eNeuro 2016;3:ENEURO.0085-15.2016.
Gutzmann A, Ergül N, Grossmann R, Schultz C, Wahle P, Engelhardt M. A period of structural plasticity at the axon initial segment in developing visual cortex. Front Neuroanat 2014;8:11.
Ha SR, Rasband MN. The SIZ of pain. Neuron 2019;102:709–11.
Hamada MS, Goethals S, de Vries SI, Brette R, Kole MHP. Covariation of axon initial segment location and dendritic tree normalizes the somatic action potential. Proc Natl Acad Sci U S A 2016;113:14841–6.
Hargreaves K, Dubner R, Brown F, Flores C, Joris J. A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. PAIN 1988;32:77–88.
Häring M, Zeisel A, Hochgerner H, Rinwa P, Jakobsson JET, Lönnerberg P, la Manno G, Sharma N, Borgius L, Kiehn O, Lagerström MC, Linnarsson S, Ernfors P. Neuronal atlas of the dorsal horn defines its architecture and links sensory input to transcriptional cell types. Nat Neurosci 2018;21:6869–880.
He X, Liu P, Zhang X, Jiang Z, Gu N, Wang Q, Lu Y. Molecular and electrophysiological characterization of dorsal horn neurons in a GlyT2-iCre-tdTomato mouse line. J Pain Res 2021;14:907–21.
Hines ML, Carnevale NT. The NEURON simulation environment. Neural Comput 1997;9:1179–209.
Hinman JD, Rasband MN, Carmichael ST. Remodeling of the axon initial segment after focal cortical and white matter stroke. Stroke 2013;44:182–9.
Huang CY-M, Rasband MN. Axon initial segments: structure, function, and disease. Ann N Y Acad Sci 2018;1420:46–61.
Hucho T, Levine JD. Signaling pathways in sensitization: toward a nociceptor cell biology. Neuron 2007;55:365–76.
Hughes DI, Todd AJ. Central nervous system targets: inhibitory interneurons in the spinal cord. Neurotherapeutics 2020;17:874–85.
Jamann N, Dannehl D, Lehmann N, Wagener R, Thielemann C, Schultz C, Staiger J, Kole MHP, Engelhardt M. Sensory input drives rapid homeostatic scaling of the axon initial segment in mouse barrel cortex. Nat Commun 2021;12:23.
Jamann N, Jordan M, Engelhardt M. Activity-dependent axonal plasticity in sensory systems. Neuroscience 2018;368:268–82.
Jenerick H. Phase plane trajectories of the muscle spike potential. Biophysical J 1963;3:363–77.
Jin X, Gereau RW. Acute p38-mediated modulation of tetrodotoxin-resistant sodium channels in mouse sensory neurons by tumor necrosis Factor-alpha. J Neurosci 2006;26:246–55.
Jørgensen HS, Jensen DB, Dimintiyanova KP, Bonnevie VS, Hedegaard A, Lehnhoff J, Moldovan M, Grondahl L, Meehan CF. Increased axon initial segment length results in increased Na+ currents in spinal motoneurones at symptom onset in the G127X SOD1 mouse model of amyotrophic lateral sclerosis. Neuroscience 2021;468:247–64.
Kohno T, Moore KA, Baba H, Woolf CJ. Peripheral nerve injury alters excitatory synaptic transmission in lamina II of the rat dorsal horn. J Physiol 2003;548:131–8.
Kole MH, Brette R. The electrical significance of axon location diversity. Curr Opin Neurobiol 2018;51:52–9.
Kole MHP, Ilschner SU, Kampa BM, Williams SR, Ruben PC, Stuart GJ. Action potential generation requires a high sodium channel density in the axon initial segment. Nat Neurosci 2008;11:178–86.
Kole MHP, Stuart GJ. Signal processing in the axon initial segment. Neuron 2012;73:235–47.
Kordeli E, Lambert S, Bennett V. AnkyrinG. A new ankyrin gene with neural-specific isoforms localized at the axonal initial segment and node of Ranvier. J Biol Chem 1995;270:2352–9.
Kuba H, Ishii TM, Ohmori H. Axonal site of spike initiation enhances auditory coincidence detection. Nature 2006;444:1069–72.
Kuba H, Oichi Y, Ohmori H. Presynaptic activity regulates Na(+) channel distribution at the axon initial segment. Nature 2010;465:1075–8.
Lee KY, Ratté S, Prescott SA. Excitatory neurons are more disinhibited than inhibitory neurons by chloride dysregulation in the spinal dorsal horn. Elife 2019;8:e49753.
Lennertz RC, Kossyreva EA, Smith AK, Stucky CL. TRPA1 mediates mechanical sensitization in nociceptors during inflammation. PLoS One 2012;7:e43597.
Leterrier C. The axon initial segment: an updated viewpoint. J Neurosci 2018;38:2135–45.
Lezmy J, Gelman H, Katsenelson M, Styr B, Tikochinsky E, Lipinsky M, Peretz A, Slutsky I, Attali B. M-current inhibition in hippocampal excitatory neurons triggers intrinsic and synaptic homeostatic responses at different temporal scales. J Neurosci 2020;40:3694–706.
Lezmy J, Lipinsky M, Khrapunsky Y, Patrich E, Shalom L, Peretz A, Fleidervish IA, Attali B. M-current inhibition rapidly induces a unique CK2-dependent plasticity of the axon initial segment. Proc Natl Acad Sci U S A 2017;114:E10234–43.
Li J, Kritzer E, Craig PE, Baccei ML. Aberrant synaptic integration in Adult lamina I projection neurons following neonatal tissue damage. J Neurosci 2015;35:2438–51.
Lipkin AM, Cunniff MM, Spratt PWE, Lemke SM, Bender KJ. Functional microstructure of CaV-mediated calcium signaling in the axon initial segment. J Neurosci 2021;41:3764–76.
Lorincz A, Nusser Z. Cell-Type-Dependent molecular composition of the axon initial segment. J Neurosci 2008;28:14329–40.
Lu Y, Doroshenko M, Lauzadis J, Kanjiya MP, Rebecchi MJ, Kaczocha M, Puopolo M. Presynaptic inhibition of primary nociceptive signals to dorsal horn lamina I neurons by dopamine. J Neurosci 2018;38:8809–21.
Melnick IV. Voltage-Dependent behavior of delayed-firing neurons in the rat substantia gelatinosa. Neurophysiology 2011;42:239–43.
Melnick IV, Santos SFA, Szokol K, Szûcs P, Safronov BV. Ionic basis of tonic firing in spinal substantia gelatinosa neurons of rat. J Neurophysiol 2004;91:646–55.
Punnakkal P, von Schoultz C, Haenraets K, Wildner H, Zeilhofer HU. Morphological, biophysical and synaptic properties of glutamatergic neurons of the mouse spinal dorsal horn. J Physiol 2014;592:759–76.
Rall W. Branching dendritic trees and motoneuron membrane resistivity. Exp Neurol 1959;1:491–527.
Rall W. Time constants and electrotonic length of membrane cylinders and neurons. Biophysical J 1969;9:1483–508.
Rotterman TM, Carrasco DI, Housley SN, Nardelli P, Powers RK, Cope TC. Axon initial segment geometry in relation to motoneuron excitability. PLoS One 2021;16:e0259918.
Sasaki T. The axon as a unique computational unit in neurons. Neurosci Res 2013;75:83–8.
Shevchuk DP, Agashkov KS, Bilan PV, Voitenko NV. Spontaneous synaptic activity in projection neurons of lamina I of the isolated rat lumbar spinal cord: effect of peripheral inflammation. Neurophysiology 2017;49:4301–4.
Sorkin LS, Xiao WH, Wagner R, Myers RR. Tumour necrosis factor-α induces ectopic activity in nociceptive primary afferent fibres. Neuroscience 1997;81:255–62.
Sun X, Wu Y, Gu M, Liu Z, Ma Y, Li J, Zhang Y. Selective filtering defect at the axon initial segment in Alzheimer's disease mouse models. Proc Natl Acad Sci U S A 2014;111:14271–6.
Tal M, Devor M. Ectopic discharge in injured nerves: comparison of trigeminal and somatic afferent. Brain Res 1992;579:148–51.
Tashima R, Koga K, Yoshikawa Y, Sekine M, Watanabe M, Tozaki-Saitoh H, Furue H, Yasaka T, Tsuda M. A subset of spinal dorsal horn interneurons crucial for gating touch-evoked pain-like behavior. Proc Natl Acad Sci U S A 2021;118:e2021220118.
Telenczuk M, Fontaine B, Brette R. The basis of sharp spike onset in standard biophysical models. PLoS One 2017;12:e0175362.
Todd AJ. Neuronal circuitry for pain processing in the dorsal horn. Nat Rev Neurosci 2010;11:823–36.
Wercberger R, Basbaum AI. Spinal cord projection neurons: a superficial, and also deep analysis. Curr Opin Physiol 2019;11:109–15.
Yamada R, Kuba H. Structural and functional plasticity at the axon initial segment. Front Cell Neurosci 2016;10:250.
Yarmolinsky DA, Peng Y, Pogorzala LA, Rutlin M, Hoon MA, Zuker CS. Coding and plasticity in the mammalian thermosensory system. Neuron 2016;92:1079–92.
Yermakov LM, Drouet DE, Griggs RB, Elased KM, Susuki K. Type 2 diabetes leads to axon initial segment shortening in db/db mice. Front Cell Neurosci 2018;12:146.
Zeilhofer HU, Zeilhofer UB. Spinal dis-inhibition in inflammatory pain. Neurosci Lett 2008;437:170–4.
Zhang H, Li Y, Yang Q, Liu XG, Dougherty PM. Morphological and physiological plasticity of spinal lamina II GABA neurons is induced by sciatic nerve chronic constriction injury in mice. Front Cell Neurosci 2018;12:143.