Abstract
Motoneurons have long been considered as the final common pathway of the nervous system, transmitting the neural impulses that are transduced into action.
While many studies have focussed on the inputs that motoneurons receive from local circuits within the spinal cord and from other parts of the CNS, relatively few have investigated the targets of local axonal projections from motoneurons themselves, with the notable exception of those contacting Renshaw cells or other motoneurons.
Recent research has not only characterised the detailed features of the excitatory connections between motoneurons and Renshaw cells but has also established that Renshaw cells are not the only target of motoneurons axons within the spinal cord. Motoneurons also form synaptic contacts with other motoneurons as well as with a subset of ventrally located V3 interneurons. These findings indicate that motoneurons cannot be simply viewed as the last relay station delivering the command drive to muscles, but perform an active role in the generation and modulation of motor patterns.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Alvarez FJ, Dewey DE, McMillin P, Fyffe RE (1999) Distribution of cholinergic contacts on Renshaw cells in the rat spinal cord: a light microscopic study. J Physiol 515(Pt 3):787–797
Bhumbra GS, Beato M (2018) Recurrent excitation between motoneurones propagates across segments and is purely glutamatergic. PLoS Biol 16. https://doi.org/10.1371/journal.pbio.2003586
Bhumbra GS, Moore NJ, Moroni M, Beato M (2012) Co-release of GABA does not occur at glycinergic synapses onto lumbar motoneurons in juvenile mice. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3309924/. Accessed 25 Oct 2019
Bhumbra GS, Bannatyne BA, Watanabe M, Todd AJ, Maxwell DJ, Beato M (2014) The recurrent case for the Renshaw cell. J Neurosci 34:12919–12932
Bonnot A, Chub N, Pujala A, O’Donovan MJ (2009) Excitatory actions of ventral root stimulation during network activity generated by the disinhibited neonatal mouse spinal cord. J Neurophysiol 101:2995–3011. https://doi.org/10.1152/jn.90740.2008
Brownstone RM, Bui TV, Stifani N (2015) Spinal circuits for motor learning. Curr Opin Neurobiol 33:166–173. https://doi.org/10.1016/j.conb.2015.04.007
Chang Q, Gonzalez M, Pinter MJ, Balice-Gordon RJ (1999) Gap junctional coupling and patterns of connexin expression among neonatal rat lumbar spinal motor neurons. J Neurosci 19:10813–10828
Chery N, De Koninck Y (1999) Junctional versus extrajunctional glycine and GABA(A) receptor-mediated IPSCs in identified lamina I neurons of the adult rat spinal cord. J Neurosci 19:7342–7355
Chopek JW, Nascimento F, Beato M, Brownstone RM, Zhang Y (2018) Sub-populations of spinal V3 interneurons form focal modules of layered pre-motor microcircuits. Cell Rep 25. https://doi.org/10.1016/j.celrep.2018.08.095
Coggeshall RE (1980) Law of separation of function of the spinal roots. Physiol Rev 60:716–755
Cullheim S, Kellerth JO (1978) A morphological study of the axons and recurrent axon collaterals of cat alpha-motoneurones supplying different functional types of muscle unit. J Physiol 281:301–313. https://doi.org/10.1113/jphysiol.1978.sp012423
Cullheim S, Kellerth JO, Conradi S (1977) Evidence for direct synaptic interconnections between cat spinal alpha-motoneurons via the recurrent axon collaterals: a morphological study using intracellular injection of horseradish peroxidase. Brain Res 132:1–10
Cullheim S, Fleshman JW, Glenn LL, Burke RE (1987) Three-dimensional architecture of dendritic trees in type-identified alpha-motoneurons. J Comp Neurol 255:82–96. https://doi.org/10.1002/cne.902550107
Dale H (1935) Pharmacology and nerve-endings (Walter Ernest Dixon Memorial Lecture). Proc R Soc Med 28:319–332
Danner SM, Shevtsova NA, Alain F, Rybak IA (2017) Computational modeling of spinal circuits controlling limb coordination and gaits in quadrupeds. eLife 6. Cambridge. https://doi.org/10.7554/eLife.31050
Delpy A, Allain A-E, Meyrand P, Branchereau P (2008) NKCC1 cotransporter inactivation underlies embryonic development of chloride-mediated inhibition in mouse spinal motoneuron. J Physiol 586:1059–1075. https://doi.org/10.1113/jphysiol.2007.146993
Dreifuss JJ, Kelly JS (1972) Recurrent inhibition of antidromically identified rat supraoptic neurones. J Physiol 220:87–103. https://doi.org/10.1113/jphysiol.1972.sp009696
Dugue GP, Dumoulin A, Triller A, Dieudonne S (2005) Target-dependent use of co-released inhibitory transmitters at central synapses. J Neurosci 25:6490–6498
Eccles JC, Fatt P, Koketsu K (1954) Cholinergic and inhibitory synapses in a pathway from motor-axon collaterals to motoneurones. J Physiol Lond 126:524–562
Eccles JC, Jones RV, Paton WDM (1976) From electrical to chemical transmission in the central nervous system: the closing address of the Sir Henry Dale Centennial Symposium Cambridge, 19 September 1975. Notes Rec R Soc Lond 30:219–230. https://doi.org/10.1098/rsnr.1976.0015
Enjin A, Rabe N, Nakanishi ST, Vallstedt A, Gezelius H, Memic F, Lind M, Hjalt T, Tourtellotte WG, Bruder C, Eichele G, Whelan PJ, Kullander K (2010) Identification of novel spinal cholinergic genetic subtypes disclose Chodl and Pitx2 as markers for fast motor neurons and partition cells. J Comp Neurol 518:2284–2304. https://doi.org/10.1002/cne.22332
Enjin A, Perry S, Hilscher MM, Nagaraja C, Larhammar M, Gezelius H, Eriksson A, Leão KE, Kullander K (2017) Developmental disruption of recurrent inhibitory feedback results in compensatory adaptation in the Renshaw cell–motor neuron circuit. J Neurosci 37:5634–5647. https://doi.org/10.1523/JNEUROSCI.0949-16.2017
Falgairolle M, Puhl JG, Pujala A, Liu W, O’Donovan MJ (2017) Motoneurons regulate the central pattern generator during drug-induced locomotor-like activity in the neonatal mouse. Elife 6:e26622–e26622. https://doi.org/10.7554/eLife.26622
Fulton BP, Miledi R, Takahashi T (1980) Electrical synapses between motoneurons in the spinal cord of the newborn rat. Proc R Soc Lond B Biol Sci 208:115–120
Henneman E (1957) Relation between size of neurons and their susceptibility to discharge. Science 126:1345–1347. https://doi.org/10.1126/science.126.3287.1345
Herzog E, Landry M, Buhler E, Bouali-Benazzouz R, Legay C, Henderson CE, Nagy F, Dreyfus P, Giros B, El MS (2004) Expression of vesicular glutamate transporters, VGLUT1 and VGLUT2, in cholinergic spinal motoneurons. Eur J Neurosci 20:1752–1760. https://doi.org/10.1111/j.1460-9568.2004.03628.x
Hinckley CA, Ziskind-Conhaim L (2006) Electrical coupling between locomotor-related excitatory interneurons in the mammalian spinal cord. J Neurosci 26:8477–8483. https://doi.org/10.1523/JNEUROSCI.0395-06.2006
Hultborn H, Pierrot-Deseilligny E (1979) Input-output relations in the pathway of recurrent inhibition to motoneurones in the cat. J Physiol 297:267–287
Hultborn H, Lindstrom S, Wigstrom H (1979) On the function of recurrent inhibition in the spinal cord. Exp Brain Res 37:399–403
Hultborn H, Katz R, Mackel R (1988a) Distribution of recurrent inhibition within a motor nucleus. II. Amount of recurrent inhibition in motoneurones to fast and slow units. Acta Physiol Scand 134:363–374. https://doi.org/10.1111/j.1748-1716.1988.tb08502.x
Hultborn H, Lipski J, Mackel R, Wigstrom H (1988b) Distribution of recurrent inhibition within a motor nucleus. I. Contribution from slow and fast motor units to the excitation of Renshaw cells. Acta Physiol Scand 134:347–361. https://doi.org/10.1111/j.1748-1716.1988.tb08503.x
Ichinose T, Miyata Y (1998) Recurrent excitation of motoneurons in the isolated spinal cord of newborn rats detected by whole-cell recording. Neurosci Res 31:179–187
Jankowska E, Hammar I (2013) Interactions between spinal interneurons and ventral spinocerebellar tract neurons. J Physiol 591:5445–5451. https://doi.org/10.1113/jphysiol.2012.248740
Jefferys JG (1995) Nonsynaptic modulation of neuronal activity in the brain: electric currents and extracellular ions. Physiol Rev 75:689–723. https://doi.org/10.1152/physrev.1995.75.4.689
Jiang J, Alstermark B (2015) Not GABA but glycine mediates segmental, propriospinal, and bulbospinal postsynaptic inhibition in adult mouse spinal forelimb motor neurons. J Neurosci 35:1991–1998. https://doi.org/10.1523/JNEUROSCI.1627-14.2015
Jiang ZG, Shen E, Wang MY, Dun NJ (1991) Excitatory postsynaptic potentials evoked by ventral root stimulation in neonate rat motoneurons in vitro. J Neurophysiol 65:57–66
Jonas P, Bischofberger J, Sandkuhler J (1998) Corelease of two fast neurotransmitters at a central synapse. Science 281:419–424
Krashia P, Ledonne A, Nobili A, Cordella A, Errico F, Usiello A, D’Amelio M, Mercuri NB, Guatteo E, Carunchio I (2016) Persistent elevation of D-aspartate enhances NMDA receptor-mediated responses in mouse substantia nigra pars compacta dopamine neurons. Neuropharmacology 103:69–78. https://doi.org/10.1016/j.neuropharm.2015.12.013
Kraus T, Neuhuber WL, Raab M (2004) Vesicular glutamate transporter 1 immunoreactivity in motor endplates of striated esophageal but not skeletal muscles in the mouse. Neurosci Lett 360:53–56. https://doi.org/10.1016/j.neulet.2004.02.039
Lamotte d’Incamps B, Ascher P (2008) Four excitatory postsynaptic ionotropic receptors coactivated at the motoneuron-Renshaw cell synapse. J Neurosci 28:14121–14131. https://doi.org/10.1523/JNEUROSCI.3311-08.2008
Lamotte d’Incamps B, Ascher P (2014) High affinity and low affinity heteromeric nicotinic acetylcholine receptors at central synapses. J Physiol Lond 592:4131–4136. https://doi.org/10.1113/jphysiol.2014.273128
Lamotte d’Incamps B, Bhumbra GSS, Foster JDD, Beato M, Ascher P, Lamotte d’Incamps B, Bhumbra GSS, Foster JDD, Beato M, Ascher P (2017) Segregation of glutamatergic and cholinergic transmission at the mixed motoneuron Renshaw cell synapse. Sci Rep 7:4037–4037. https://doi.org/10.1038/s41598-017-04266-8
Leng G, Dyball REJ (1983) Intercommunication in the rat supraoptic nucleus. Q J Exp Physiol 68:493–504. https://doi.org/10.1113/expphysiol.1983.sp002742
Leroy F, d’Incamps BL, Imhoff-Manuel RD, Zytnicki D (2014) Early intrinsic hyperexcitability does not contribute to motoneuron degeneration in amyotrophic lateral sclerosis. elife 3:e04046–e04046. https://doi.org/10.7554/eLife.04046
Lu T, Rubio ME, Trussell LO (2008) Glycinergic transmission shaped by the corelease of GABA in a mammalian auditory synapse. Neuron 57:524–535
Machacek DW, Hochman S (2006) Noradrenaline unmasks novel self-reinforcing motor circuits within the mammalian spinal cord. J Neurosci 26:5920–5928. https://doi.org/10.1523/JNEUROSCI.4623-05.2006
Maltenfort MG, Heckman CJ, Rymer WZ (1998) Decorrelating actions of Renshaw interneurons on the firing of spinal motoneurons within a motor nucleus: a simulation study. J Neurophysiol 80:309–323
Marchetti C, Beato M, Nistri A (2001a) Alternating rhythmic activity induced by dorsal root stimulation in the neonatal rat spinal cord in vitro. J Physiol 530:105–112. https://doi.org/10.1111/j.1469-7793.2001.0105m.x
Marchetti C, Beato M, Nistri A (2001b) Evidence for increased extracellular K+ as an important mechanism for dorsal root induced alternating rhythmic activity in the neonatal rat spinal cord in vitro. Neurosci Lett 304:77–80. https://doi.org/10.1016/S0304-3940(01)01777-3
McCurdy ML, Hamm TM (1992) Recurrent collaterals of motoneurons projecting to distal muscles in the cat hindlimb. J Neurophysiol 67:1359–1366. https://doi.org/10.1152/jn.1992.67.5.1359
McCurdy ML, Hamm TM (1994) Topography of recurrent inhibitory postsynaptic potentials between individual motoneurons in the cat. J Neurophysiol 72:214–226. https://doi.org/10.1152/jn.1994.72.1.214
Meister B, Arvidsson U, Zhang X, Jacobsson G, Villar MJ, Hökfelt T (1993) Glutamate transporter mRNA and glutamate-like immunoreactivity in spinal motoneurones. Neuroreport 5:337–340. https://doi.org/10.1097/00001756-199312000-00040
Mentis GZ, Alvarez FJ, Bonnot A, Richards DS, Gonzalez-Forero D, Zerda R, O’Donovan MJ (2005) Noncholinergic excitatory actions of motoneurons in the neonatal mammalian spinal cord. Proc Natl Acad Sci 102:7344–7349
Moore NJ, Bhumbra GS, Foster JD, Beato M (2015) Synaptic connectivity between Renshaw cells and motoneurons in the recurrent inhibitory circuit of the spinal cord. J Neurosci. https://doi.org/10.1523/jneurosci.2541-15.2015
Muller D, Cherukuri P, Henningfeld K, Poh CH, Wittler L, Grote P, Schluter O, Schmidt J, Laborda J, Bauer SR, Brownstone RM, Marquardt T (2014) Dlk1 promotes a fast motor neuron biophysical signature required for peak force execution. Science 343:1264–1266. https://doi.org/10.1126/science.1246448
Nishimaru H, Restrepo CE, Ryge J, Yanagawa Y, Kiehn O (2005) Mammalian motor neurons corelease glutamate and acetylcholine at central synapses. Proc Natl Acad Sci 102:5245–5249
Oliveira ALR, Hydling F, Olsson E, Shi T, Edwards RH, Fujiyama F, Kaneko T, Hökfelt T, Cullheim S, Meister B (2003) Cellular localization of three vesicular glutamate transporter mRNAs and proteins in rat spinal cord and dorsal root ganglia. Synapse 50:117–129. https://doi.org/10.1002/syn.10249
Patneau DK, Mayer ML (1990) Structure-activity relationships for amino acid transmitter candidates acting at N-methyl-D-aspartate and quisqualate receptors. J Neurosci 10:2385–2399. https://doi.org/10.1523/JNEUROSCI.10-07-02385.1990
Perrins R, Roberts A (1995) Cholinergic and electrical synapses between synergistic spinal motoneurones in the Xenopus laevis embryo. J Physiol 485(Pt 1):135–144
Perry S, Gezelius H, Larhammar M, Hilscher MM, Lamotte d’Incamps B, Leao KE, Kullander K (2015) Firing properties of Renshaw cells defined by Chrna2 are modulated by hyperpolarizing and small conductance ion currents Ih and ISK. Eur J Neurosci 41:889–900. https://doi.org/10.1111/ejn.12852
Personius KE, Chang Q, Mentis GZ, O’Donovan MJ, Balice-Gordon RJ (2007) Reduced gap junctional coupling leads to uncorrelated motor neuron firing and precocious neuromuscular synapse elimination. Proc Natl Acad Sci U S A 104:11808–11813. https://doi.org/10.1073/pnas.0703357104
Rash JE, Dillman RK, Bilhartz BL, Duffy HS, Whalen LR, Yasumura T (1996) Mixed synapses discovered and mapped throughout mammalian spinal cord. Proc Natl Acad Sci U S A 93:4235–4239
Renshaw B (1946) Central effects of centripetal impulses in axons of spinal ventral roots. J Neurophysiol 9:191–204
Richards DS, Griffith RW, Romer SH, Alvarez FJ (2014) Motor axon synapses on renshaw cells contain higher levels of aspartate than glutamate. PLoS One 9:e97240–e97240. https://doi.org/10.1371/journal.pone.0097240
Ross HG, Cleveland S, Haase J (1975) Contribution of single motoneurons to renshaw cell activity. Neurosci Lett 1:105–108
Ross HG, Cleveland S, Haase J (1976) Quantitative relation between discharge frequencies of a Renshaw cell and an intracellularly depolarized motoneuron. Neurosci Lett 3:129–132
Ryall RW, Piercey MF (1971) Excitation and inhibition of Renshaw cells by impulses in peripheral afferent nerve fibers. J Neurophysiol 34:242–251. https://doi.org/10.1152/jn.1971.34.2.242
Schäfer MK-H, Varoqui H, Defamie N, Weihe E, Erickson JD (2002) Molecular cloning and functional identification of mouse vesicular glutamate transporter 3 and its expression in subsets of novel excitatory neurons. J Biol Chem 277:50734–50748. https://doi.org/10.1074/jbc.M206738200
Schneider SP, Fyffe RE (1992) Involvement of GABA and glycine in recurrent inhibition of spinal motoneurons. J Neurophysiol 68:397–406
Sherrington C (1906) The integrative action of the nervous system. Yale University Press, New Haven
Singer JH, Talley EM, Bayliss DA, Berger AJ (1998) Development of glycinergic synaptic transmission to rat brain stem motoneurons. J Neurophysiol 80:2608–2620
Song J, Ampatzis K, Björnfors ER, El Manira A (2016) Motor neurons control locomotor circuit function retrogradely via gap junctions. Nature. https://doi.org/10.1038/nature16497
Stepien AE, Tripodi M, Arber S (2010) Monosynaptic rabies virus reveals premotor network organization and synaptic specificity of cholinergic partition cells. Neuron 68:456–472. https://doi.org/10.1016/j.neuron.2010.10.019
Tripodi M, Stepien AE, Arber S (2011) Motor antagonism exposed by spatial segregation and timing of neurogenesis. Nature 479:61–66. https://doi.org/10.1038/nature10538
Van Keulen L (1981) Autogenetic recurrent inhibition of individual spinal motoneurones of the cat. Neurosci Lett 21:297–300
Wærhaug O, Ottersen OP (1993) Demonstration of glutamate-like immunoreactivity at rat neuromuscular junctions by quantitative electron microscopic immunocytochemistry. Anat Embryol 188:501–513. https://doi.org/10.1007/BF00190144
Walton KD, Navarrete R (1991) Postnatal changes in motoneurone electrotonic coupling studied in the in vitro rat lumbar spinal cord. J Physiol 433:283–305
Windhorst U (1996) On the role of recurrent inhibitory feedback in motor control. Prog Neurobiol 49:517–587
Zhang Y, Narayan S, Geiman E, Lanuza GM, Velasquez T, Shanks B, Akay T, Dyck J, Pearson K, Gosgnach S, Fan CM, Goulding M (2008) V3 spinal neurons establish a robust and balanced locomotor rhythm during walking. Neuron 60:84–96
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2022 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Beato, M., Bhumbra, G. (2022). Synaptic Projections of Motoneurons Within the Spinal Cord. In: O'Donovan, M.J., Falgairolle, M. (eds) Vertebrate Motoneurons. Advances in Neurobiology, vol 28. Springer, Cham. https://doi.org/10.1007/978-3-031-07167-6_7
Download citation
DOI: https://doi.org/10.1007/978-3-031-07167-6_7
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-031-07166-9
Online ISBN: 978-3-031-07167-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)