Firing properties of Renshaw cells defined by Chrna2 are modulated by hyperpolarizing and small conductance ion currents Ih and ISK
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Renshaw cells in the spinal cord ventral horn regulate motoneuron output through recurrent inhibition. Renshaw cells can be identified in vitro using anatomical and cellular criteria; however, their functional role in locomotion remains poorly defined because of the difficulty of functionally isolating Renshaw cells from surrounding motor circuits. Here we aimed to investigate whether the cholinergic nicotinic receptor alpha2 (Chrna2) can be used to identify Renshaw cells (RC s α2) in the mouse spinal cord. Immunohistochemistry and electrophysiological characterization of passive and active RC s α2 properties confirmed that neurons genetically marked by the Chrna2‐Cre mouse line together with a fluorescent reporter mouse line are Renshaw cells. Whole‐cell patch‐clamp recordings revealed that RC s α2 constitute an electrophysiologically stereotyped population with a resting membrane potential of −50.5 ± 0.4 mV and an input resistance of 233.1 ± 11 MΩ. We identified a ZD 7288‐sensitive hyperpolarization‐activated cation current (Ih) in all RC s α2, contributing to membrane repolarization but not to the resting membrane potential in neonatal mice. Additionally, we found RC s α2 to express small calcium‐activated potassium currents (ISK) that, when blocked by apamin, resulted in a complete attenuation of the afterhyperpolarisation potential, increasing cellular firing frequency. We conclude that RC s α2 can be genetically targeted through their selective Chrna2 expression and that they display currents known to modulate rebound excitation and firing frequency. The genetic identification of Renshaw cells and their electrophysiological profile is required for genetic and pharmacological manipulation as well as computational simulations with the aim to understand their functional role.
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Inhib-26 was the most robust ventral cluster and expressed the Renshaw marker genes Chrna2, Chrna7, and Calb1, suggesting it corresponded to Renshaw cells.
“Inhib-26 was the most robust ventral cluster and expressed the Renshaw marker genes Chrna2, Chrna7, and Calb1, suggesting that this cluster corresponded to Renshaw cells89,90.”
From A harmonized atlas of mouse spinal cord cell types and their spatial organization (2021) · cites this paper as [90]
Cites
Cholinergic and inhibitory synapses in a pathway from motor‐axon collaterals to motoneurones
Eccles, J. C., Fatt, P., & KOKETSU, K. (1954) · The Journal of Physiology · doi:10.1113/jphysiol.1954.sp005226 · Cited by 1,198 · see citing works
Queer Current and Pacemaker: The Hyperpolarization-Activated Cation Current in Neurons
Pape, H.-C. (1996) · Annual Review of Physiology · doi:10.1146/annurev.ph.58.030196.001503 · Cited by 1,152 · see citing works
Molecular Diversity of K<sup>+</sup> Channels
COETZEE, W. A., AMARILLO, Y., CHIU, J., CHOW, A., LAU, D., McCORMACK, T., MORENA, H., NADAL, M. S., OZAITA, A., POUNTNEY, D., et al. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb11293.x · Cited by 1,095 · see citing works
A Developmental Switch in the Response of DRG Neurons to ETS Transcription Factor Signaling
Hippenmeyer, S., Pecho‐Vrieseling, E., Sigrist, M., Portmann, T., Laengle, C., Ladle, D. R., & Arber, S. (2005) · PLoS Biology · doi:10.1371/journal.pbio.0030159 · Cited by 1,059 · see citing works
Santoro, B., Chen, S., Lüthi, A., Pavlidis, P., Shumyatsky, G. P., Tibbs, G. R., & Siegelbaum, S. A. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-14-05264.2000 · Cited by 600 · see citing works
Nicotine binding and nicotinic receptor subunit RNA after chronic nicotine treatment
Marks, M., Pauly, Jr., Gross, S., Deneris, E., Hermans-Borgmeyer, I., Heinemann, S., & Collins, A. (1992) · The Journal of Neuroscience · doi:10.1523/jneurosci.12-07-02765.1992 · Cited by 551 · see citing works
Maccaferri, G., & McBain, C. J. (1996) · The Journal of Physiology · doi:10.1113/jphysiol.1996.sp021754 · Cited by 503 · see citing works
Precise Localization of Renshaw Cells with a New Marking Technique
THOMAS, R. C., & Wilson, V. J. (1965) · Nature · doi:10.1038/206211b0 · Cited by 470 · see citing works
Small-Conductance Ca2+-Activated K+Channels: Form and Function
Adelman, J. P., Maylie, J., & Sah, P. (2011) · Annual Review of Physiology · doi:10.1146/annurev-physiol-020911-153336 · Cited by 454 · see citing works
Lüthi, A., & McCormick, D. A. (1998) · Neuron · doi:10.1016/s0896-6273(00)80509-7 · Cited by 417 · see citing works
Gephyrin: a master regulator of neuronal function?
Tyagarajan, S. K., & Fritschy, J. (2014) · Nature reviews. Neuroscience · doi:10.1038/nrn3670 · Cited by 417 · see citing works
V1 spinal neurons regulate the speed of vertebrate locomotor outputs
Gosgnach, S., Lanuza, G. M., Butt, S. J. B., Saueressig, H., Zhang, Y., Velasquez, T., Riethmacher, D., Callaway, E. M., Kiehn, O., & Goulding, M. (2006) · Nature · doi:10.1038/nature04545 · Cited by 405 · see citing works
Grudt, T. J., & Perl, E. R. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2001.012890 · Cited by 402 · see citing works
Identification of Four Classes of Brain Nicotinic Receptors Using β2 Mutant Mice
Zoli, M., Léna, C., Picciotto, M. R., & Changeux, J. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-12-04461.1998 · Cited by 401 · see citing works
Identification of four classes of brain nicotinic receptors using beta2 mutant mice.
Zoli, M., Léna, C., Picciotto, M. R., & Changeux, J. (1998) · PubMed Central · doi:10.1523/jneurosci.18-12-04461.1996 · Cited by 387 · see citing works
OLM interneurons differentially modulate CA3 and entorhinal inputs to hippocampal CA1 neurons
Leão, R. N., Mikulovic, S., Leão, K. E., Munguba, H., Gezelius, H., Enjin, A., Patra, K., Eriksson, A., Loew, L. M., Tort, A. B. L., et al. (2012) · Nature Neuroscience · doi:10.1038/nn.3235 · Cited by 359 · see citing works
Self-citationNeurophysiology of HCN channels: From cellular functions to multiple regulations
He, C., Chen, F., Li, B., & Hu, Z. (2013) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.10.001 · Cited by 351 · see citing works
Bond, C. T. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.0182-04.2004 · Cited by 291 · see citing works
Postnatal phenotype and localization of spinal cord V1 derived interneurons
Alvarez, F. J., Jonas, P. C., Sapir, T., Hartley, R., Berrocal, M. C., Geiman, E. J., Todd, A. J., & Goulding, M. (2005) · Journal of Comparative Neurology · doi:10.1002/cne.20711 · Cited by 243 · see citing works
Edgerton, J. R., & Reinhart, P. H. (2003) · The Journal of Physiology · doi:10.1111/j.1469-7793.2003.00053.x · Cited by 237 · see citing works
The fractions of short- and long-range connections in the visual cortex
Stepanyants, A., Martinez, L. M., Ferecskó, A. S., & Kisvárday, Z. F. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810390106 · Cited by 208 · see citing works
Key mechanisms for setting the input–output gain across the motoneuron pool
Hultborn, H., Brownstone, R. M., Toth, T. I., & Gossard, J. (2004) · Progress in brain research · doi:10.1016/s0079-6123(03)43008-2 · Cited by 205 · see citing works
Mechanisms underlying the early phase of spike frequency adaptation in mouse spinal motoneurones
Miles, G. B., Dai, Y., & Brownstone, R. M. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.086033 · Cited by 189 · see citing works
Pax6 and Engrailed 1 Regulate Two Distinct Aspects of Renshaw Cell Development
Sapir, T., Geiman, E. J., Wang, Z., Velasquez, T., Mitsui, S., Yoshihara, Y., Frank, E., Álvarez, F. J., & Goulding, M. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.3187-03.2004 · Cited by 189 · see citing works
Meskenaïte, V. (1997) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19970303)379:1 · Cited by 180 · see citing works
The continuing case for the Renshaw cell
Álvarez, F. J., & Fyffe, R. E. W. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.136200 · Cited by 171 · see citing works
Ryall, R. W. (1970) · Journal of Neurophysiology · doi:10.1152/jn.1970.33.2.257 · Cited by 162 · see citing works
Ye, J. H., Zhang, J., Xiao, C., & Kong, J. (2006) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2006.06.006 · Cited by 136 · see citing works
Kiehn, O., Kjærulff, O., Tresch, M. C., & Harris‐Warrick, R. M. (2000) · Brain Research Bulletin · doi:10.1016/s0361-9230(00)00398-1 · Cited by 136 · see citing works
Enjin, A., Bernhardt, N. R., Nakanishi, S. T., Vallstedt, A., Gezelius, H., Memic, F., Lind, M., Hjalt, T. Å. H., Tourtellotte, W. G., Bruder, C. E. G., et al. (2010) · The Journal of Comparative Neurology · doi:10.1002/cne.22332 · Cited by 130 · see citing works
Self-citationRenshaw cell activity and recurrent effects on motoneurons during fictive locomotion.
McCrea, D. A., Pratt, C. A., & Jordan, L. M. (1980) · Journal of Neurophysiology · doi:10.1152/jn.1980.44.3.475 · Cited by 126 · see citing works
Functional subpopulations of V3 interneurons in the mature mouse spinal cord
Borowska, J., Jones, C. T., Zhang, H., Blacklaws, J., Goulding, M., & Zhang, Y. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.2005-13.2013 · Cited by 111 · see citing works
The Role of HCN Channels on Membrane Excitability in the Nervous System
Kase, D., & Imoto, K. (2012) · Journal of Signal Transduction · doi:10.1155/2012/619747 · Cited by 107 · see citing works
Deardorff, A. S., Romer, S. H., Deng, Z., et al. (2012) · The Journal of Physiology · doi:10.1113/jphysiol.2012.240879 · Cited by 99 · see citing works
Calbindin D28k expression in immunohistochemically identified Renshaw cells
Carr, P. A., Álvarez, F. J., Leman, E. A., & Fyffe, R. E. W. (1998) · Neuroreport · doi:10.1097/00001756-199808030-00043 · Cited by 98 · see citing works
Spinal interneurons providing input to the final common path during locomotion
Brownstone, R. M., & Bui, T. V. (2010) · Progress in brain research · doi:10.1016/b978-0-444-53613-6.00006-x · Cited by 84 · see citing works
Wu, X., Liao, L., Liu, X., Luo, F., Yang, T., & Li, C. (2012) · Channels · doi:10.4161/chan.22209 · Cited by 84 · see citing works
Primary Afferent Synapses on Developing and Adult Renshaw Cells
Mentis, G. Z., Siembab, V. C., Zerda, R., O'Donovan, M. J., & Álvarez, F. J. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.2945-06.2006 · Cited by 83 · see citing works
Ishii, K., Wong, J. K., & Sumikawa, K. (2005) · The Journal of Comparative Neurology · doi:10.1002/cne.20762 · Cited by 81 · see citing works
Alterations in the motor neuron–renshaw cell circuit in the Sod1G93A mouse model
Wootz, H., FitzSimons‐Kantamneni, E., Larhammar, M., Rotterman, T. M., Enjin, A., Patra, K., André, E., van Zundert, B., Kullander, K., & Álvarez, F. J. (2012) · The Journal of Comparative Neurology · doi:10.1002/cne.23266 · Cited by 81 · see citing works
Self-citationNishimaru, H., Restrepo, C. E., & Kiehn, O. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.5127-05.2006 · Cited by 79 · see citing works
Siembab, V. C., Smith, C., Zagoraiou, L., Berrocal, M. C., Mentis, G. Z., & Álvarez, F. J. (2010) · The Journal of Comparative Neurology · doi:10.1002/cne.22441 · Cited by 79 · see citing works
EFFECTS OF SUPRASPINAL STIMULATION ON RENSHAW CELLS BELONGING TO EXTENSOR MOTONEURONES
Haase, J., & Meulen, J. P. V. D. (1961) · Journal of Neurophysiology · doi:10.1152/jn.1961.24.5.510 · Cited by 72 · see citing works
Four Excitatory Postsynaptic Ionotropic Receptors Coactivated at the Motoneuron–Renshaw Cell Synapse
d’Incamps, B. L., & Ascher, P. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.3311-08.2008 · Cited by 69 · see citing works
González‐Forero, D., & Álvarez, F. J. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2383-04.2005 · Cited by 69 · see citing works
Khurana, S., Liu, Z., Lewis, A. S., Rosa, K., Chetkovich, D. M., & Golding, N. L. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.3882-11.2012 · Cited by 67 · see citing works
An in vitro spinal cord slice preparation for recording from lumbar motoneurons of the adult mouse
Mitra, P., & Brownstone, R. M. (2011) · Journal of Neurophysiology · doi:10.1152/jn.00558.2011 · Cited by 65 · see citing works
Hyperpolarization‐activated currents are differentially expressed in mice brainstem auditory nuclei
Leão, K. E., Leão, R. N., Sun, H. Q., et al. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.114702 · Cited by 56 · see citing works
HCN4 subunit expression in fast-spiking interneurons of the rat spinal cord and hippocampus
Hughes, D. I., Boyle, K. A., Kinnon, C. M., Bilsland, C., Quayle, J. A., Callister, R. J., & Graham, B. A. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.01.028 · Cited by 55 · see citing works
Álvarez, F. J., Benito‐Gonzalez, A., & Siembab, V. C. (2013) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12084 · Cited by 50 · see citing works
Postnatal maturation of gephyrin/glycine receptor clusters on developing Renshaw cells
Geiman, E. J., Knox, M. C., & Álvarez, F. J. (2000) · The Journal of Comparative Neurology · doi:10.1002/1096-9861(20001009)426:1 · Cited by 46 · see citing works
Renshaw, B. (1946) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1946.146.3.443 · Cited by 45 · see citing works
Liu, S., & Shipley, M. T. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.2608-08.2008 · Cited by 44 · see citing works
Griguoli, M., Maul, A., Nguyen, C., Giorgetti, A., Carloni, P., & Cherubini, E. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.2446-10.2010 · Cited by 41 · see citing works
Boehme, R., Uebele, V. N., Renger, J. J., et al. (2011) · Journal of Neurophysiology · doi:10.1152/jn.00612.2011 · Cited by 40 · see citing works
An intracellular study of Renshaw cells
Walmsley, B. D., & Tracey, D. J. (1981) · Brain Research · doi:10.1016/0006-8993(81)90818-0 · Cited by 40 · see citing works
González‐Forero, D., Pastor, Á. M., Geiman, E. J., Benítez‐Temiño, B., & Álvarez, F. J. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.3725-04.2005 · Cited by 40 · see citing works
ICI D7288, a Novel Sinoatrial Node Modulator
Marshall, P. W., Rouse, W., Briggs, I., Hargreaves, R., Mills, S. D., & McLoughlin, B. J. (1993) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-199306000-00008 · Cited by 38 · see citing works
Dourado, M., & Sargent, P. B. (2002) · Journal of Neurophysiology · doi:10.1152/jn.2002.87.6.3117 · Cited by 33 · see citing works
Kinnischtzke, A. K., Sewall, A. M., Berkepile, J. M., & Fanselow, E. E. (2012) · Frontiers in Neural Circuits · doi:10.3389/fncir.2012.00033 · Cited by 32 · see citing works
Glutamate-mediated slow synaptic currents in neonatal rat deep dorsal horn neurons in vitro
Miller, B. A., & Woolf, C. J. (1996) · Journal of Neurophysiology · doi:10.1152/jn.1996.76.3.1465 · Cited by 31 · see citing works
A decerebrate adult mouse model for examining the sensorimotor control of locomotion
Nakanishi, S. T., & Whelan, P. J. (2011) · Journal of Neurophysiology · doi:10.1152/jn.00699.2011 · Cited by 30 · see citing works
Nakanishi, S. T., & Whelan, P. J. (2010) · Journal of Neurophysiology · doi:10.1152/jn.00022.2010 · Cited by 28 · see citing works
Song, Z., Hu, J., Rudy, B., & Redman, S. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2005.12.048 · Cited by 23 · see citing works
Axonal projections of Renshaw cells in the thoracic spinal cord
Saywell, S. A., Ford, T. W., & Kirkwood, P. (2013) · Physiological Reports · doi:10.1002/phy2.161 · Cited by 16 · see citing works
Inhibitory Synaptic Modulation of Renshaw Cell Activity in the Lumbar Spinal Cord of Neonatal Mice
Nishimaru, H., Koganezawa, T., Kakizaki, M., Ebihara, T., & Yanagawa, Y. (2010) · Journal of Neurophysiology · doi:10.1152/jn.00100.2010 · Cited by 11 · see citing works
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- Authors
- Perry, S., Gezelius, H., Larhammar, M., Hilscher, M. M., Lamotte d'Incamps, B., Leao, K. E., & Kullander, K.
- Affiliations
- Uppsala University (SE)
- Neurophysique et Physiologie CNRS UMR 8119 Université Paris Descartes Paris France
- Department of Neuroscience Uppsala University Box 593 751 24 Uppsala Sweden
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2015-02-25
- Volume
- 41
- Issue
- 7
- Pages
- 889-900
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2031933366
- Cited by
- 32
- References
- 66
- Citations by year
- 2026: 2 · 2023: 3 · 2022: 5 · 2021: 4 · 2020: 1 · 2018: 9 · 2017: 5 · 2016: 3
- FWCI
- 2.46
- Type
- journal article
- Language
- en
- Open access
- green
- repositorio.ufrn.br
- Licence
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
- Americanae (AECID Library) (submittedVersion, other-oa)
- Figshare (submittedVersion, cc-by)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- Renshaw cells, CHRNA2, spinal cord ventral horn, rebound excitation, firing rate, recurrent inhibition, motor neurons, apamin, locomotion
- MeSH terms
- Action Potentials, Animals, Animals, Newborn, Apamin, Ion Channels, Lumbar Vertebrae, Mice, Inbred C57BL, Mice, Transgenic, Motor Neurons, Pyrimidines, Receptors, Nicotinic, RNA, Messenger, Spinal Cord, Spinal Nerve Roots, Tissue Distribution, Neurotransmitter Agents, Mice, 129 Strain, Renshaw Cells
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