Abstract
Locomotor movements are coordinated by a network of neurons that produces sequential muscle activation. Different motoneurons need to be recruited in an orderly manner to generate movement with appropriate speed and force. However, the mechanisms governing recruitment order have not been fully clarified. Using an in vitro juvenile/adult zebrafish brainstem-spinal cord preparation, we found that motoneurons were organized into four pools with specific topographic locations and were incrementally recruited to produce swimming at different frequencies. The threshold of recruitment was not dictated by the input resistance of motoneurons, but was instead set by a combination of specific biophysical properties and the strength of the synaptic currents. Our results provide insights into the cellular and synaptic computations governing recruitment of motoneurons during locomotion.
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References
Cope, T.C. & Pinter, M.J. The size principle: still working after all these years. News Physiol. Sci. 10, 280–286 (1995).
Henneman, E. Relation between size of neurons and their susceptibility to discharge. Science 126, 1345–1347 (1957).
Henneman, E. & Mendell, L.M. Functional organization of motoneuron pool and its inputs. in Handbook of Physiology, Sect. 1, Vol. 2 (ed. Brooks, V.E.) 423–507 (American Physiological Society, Bethesda, Maryland, 1981).
Henneman, E., Somjen, G. & Carpenter, D.O. Functional significance of cell size in spinal motoneurons. J. Neurophysiol. 28, 560–580 (1965).
Mendell, L.M. The size principle: a rule describing the recruitment of motoneurons. J. Neurophysiol. 93, 3024–3026 (2005).
Kernell, D. & Zwaagstra, B. Input conductance axonal conduction velocity and cell size among hindlimb motoneurones of the cat. Brain Res. 204, 311–326 (1981).
Binder, M.D., Heckman, C.J. & Powers, R.K. Relative strengths and distributions of different sources of synaptic input to the motoneurone pool: implications for motor unit recruitment. Adv. Exp. Med. Biol. 508, 207–212 (2002).
Heckman, C.J. & Binder, M.D. Analysis of effective synaptic currents generated by homonymous Ia afferent fibers in motoneurons of the cat. J. Neurophysiol. 60, 1946–1966 (1988).
Enoka, R.M. & Stuart, D.G. Henneman's 'size principle': current issues. Trends Neurosci. 7, 226–228 (1984).
Gustafsson, B. & Pinter, M.J. An investigation of threshold properties among cat spinal alpha-motoneurones. J. Physiol. (Lond.) 357, 453–483 (1984).
McLean, D.L., Fan, J., Higashijima, S., Hale, M.E. & Fetcho, J.R. A topographic map of recruitment in spinal cord. Nature 446, 71–75 (2007).
El Manira, A. & Grillner, S. Switching gears in the spinal cord. Nat. Neurosci. 11, 1367–1368 (2008).
McLean, D.L., Masino, M.A., Koh, I.Y., Lindquist, W.B. & Fetcho, J.R. Continuous shifts in the active set of spinal interneurons during changes in locomotor speed. Nat. Neurosci. 11, 1419–1429 (2008).
Fetcho, J.R. & McLean, D.L. Some principles of organization of spinal neurons underlying locomotion in zebrafish and their implications. Ann. NY Acad. Sci. 1198, 94–104 (2010).
McLean, D.L. & Fetcho, J.R. Spinal interneurons differentiate sequentially from those driving the fastest swimming movements in larval zebrafish to those driving the slowest ones. J. Neurosci. 29, 13566–13577 (2009).
Lewis, K.E. & Eisen, J.S. From cells to circuits: development of the zebrafish spinal cord. Prog. Neurobiol. 69, 419–449 (2003).
Myers, P.Z. Spinal motoneurons of the larval zebrafish. J. Comp. Neurol. 236, 555–561 (1985).
van Raamsdonk, W., Mos, W., Smit-Onel, M.J., van der Laarse, W.J. & Fehres, R. The development of the spinal motor column in relation to the myotomal muscle fibers in the zebrafish (Brachydanio rerio). I. Posthatching development. Anat. Embryol. (Berl.) 167, 125–139 (1983).
Westerfield, M., McMurray, J.V. & Eisen, J.S. Identified motoneurons and their innervation of axial muscles in the zebrafish. J. Neurosci. 6, 2267–2277 (1986).
Buss, R.R. & Drapeau, P. Physiological properties of zebrafish embryonic red and white muscle fibers during early development. J. Neurophysiol. 84, 1545–1557 (2000).
van Raamsdonk, W., Pool, C.W. & te Kronnie, G. Differentiation of muscle fiber types in the teleost Brachydanio rerio. Anat. Embryol. (Berl.) 153, 137–155 (1978).
van Raamsdonk, W., van't Veer, L., Veeken, K., Heyting, C. & Pool, C.W. Differentiation of muscle fiber types in the teleost Brachydanio rerio, the zebrafish. Posthatching development. Anat. Embryol. (Berl.) 164, 51–62 (1982).
Bone, Q., Kiceniuk, J. & Jones, D.R. On the role of the different fibre types in fish myotomes at intermediate swimming speeds. Fishery Bull. 76, 691–699 (1978).
Johnston, I.A. On the design of fish myotomal muscles. Mar. Freshw. Behav. Physiol. 9, 83–98 (1983).
Gabriel, J.P. et al. Locomotor pattern in the adult zebrafish spinal cord in vitro. J. Neurophysiol. 99, 37–48 (2008).
Liu, D.W. & Westerfield, M. Function of identified motoneurones and co-ordination of primary and secondary motor systems during zebra fish swimming. J. Physiol. (Lond.) 403, 73–89 (1988).
Gabriel, J.P. et al. Serotonergic modulation of locomotion in zebrafish: endogenous release and synaptic mechanisms. J. Neurosci. 29, 10387–10395 (2009).
Bhatt, D.H., McLean, D.L., Hale, M.E. & Fetcho, J.R. Grading movement strength by changes in firing intensity versus recruitment of spinal interneurons. Neuron 53, 91–102 (2007).
Heckman, C.J., Lee, R.H. & Brownstone, R.M. Hyperexcitable dendrites in motoneurons and their neuromodulatory control during motor behavior. Trends Neurosci. 26, 688–695 (2003).
Johnston, D. & Narayanan, R. Active dendrites: colorful wings of the mysterious butterflies. Trends Neurosci. 31, 309–316 (2008).
Heckman, C.J., Hyngstrom, A.S. & Johnson, M.D. Active properties of motoneurone dendrites: diffuse descending neuromodulation, focused local inhibition. J. Physiol. (Lond.) 586, 1225–1231 (2008).
El Manira, A. & Kyriakatos, A. The role of endocannabinoid signaling in motor control. Physiology (Bethesda) 25, 230–238 (2010).
Nanou, E. et al. Na+-mediated coupling between AMPA receptors and KNa channels shapes synaptic transmission. Proc. Natl. Acad. Sci. USA 105, 20941–20946 (2008).
McLean, D.L., Merrywest, S.D. & Sillar, K.T. The development of neuromodulatory systems and the maturation of motor patterns in amphibian tadpoles. Brain Res. Bull. 53, 595–603 (2000).
Sillar, K.T., Reith, C.A. & McDearmid, J.R. Development and aminergic neuromodulation of a spinal locomotor network controlling swimming in Xenopus larvae. Ann. NY Acad. Sci. 860, 318–332 (1998).
Briscoe, J. & Ericson, J. Specification of neuronal fates in the ventral neural tube. Curr. Opin. Neurobiol. 11, 43–49 (2001).
Dasen, J.S., De Camilli, A., Wang, B., Tucker, P.W. & Jessell, T.M. Hox repertoires for motor neuron diversity and connectivity gated by a single accessory factor, FoxP1. Cell 134, 304–316 (2008).
Goulding, M. Circuits controlling vertebrate locomotion: moving in a new direction. Nat. Rev. Neurosci. 10, 507–518 (2009).
Jessell, T.M. Neuronal specification in the spinal cord: inductive signals and transcriptional codes. Nat. Rev. Genet. 1, 20–29 (2000).
Dasen, J.S. & Jessell, T.M. Hox networks and the origins of motor neuron diversity. Curr. Top. Dev. Biol. 88, 169–200 (2009).
Dasen, J.S., Tice, B.C., Brenner-Morton, S. & Jessell, T.M. A Hox regulatory network establishes motor neuron pool identity and target-muscle connectivity. Cell 123, 477–491 (2005).
Vallstedt, A. et al. Different levels of repressor activity assign redundant and specific roles to Nkx6 genes in motor neuron and interneuron specification. Neuron 31, 743–755 (2001).
Cheesman, S.E., Layden, M.J., Von Ohlen, T., Doe, C.Q. & Eisen, J.S. Zebrafish and fly Nkx6 proteins have similar CNS expression patterns and regulate motoneuron formation. Development 131, 5221–5232 (2004).
Hutchinson, S.A., Cheesman, S.E., Hale, L.A., Boone, J.Q. & Eisen, J.S. Nkx6 proteins specify one zebrafish primary motoneuron subtype by regulating late islet1 expression. Development 134, 1671–1677 (2007).
Westerfield, M. The Zebrafish Book. A Guide for the Laboratory Use of the Zebrafish (Danio rerio) (University of Oregon Press, Eugene, Oregon, USA, 2000).
Acknowledgements
We thank K. Dougherty, R. Hill, S. Grillner and D. McLean for comments and critical discussion of this manuscript. This work was funded by a grant from the Swedish Research Council, European Commission (FP7, Spinal Cord Repair), Söderberg Foundation and Karolinska Institutet. J.P.G. and J.A. received post-doctoral fellowships from the German Science Foundation.
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J.P.G., J.A., K.A. and A.E.M. conceived the project and planned the experiments. J.P.G., J.A., K.A. and R.M. performed the experiments. All of the authors contributed to the analysis of the data, preparation of the figures and the writing of the manuscript.
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Gabriel, J., Ausborn, J., Ampatzis, K. et al. Principles governing recruitment of motoneurons during swimming in zebrafish. Nat Neurosci 14, 93–99 (2011). https://doi.org/10.1038/nn.2704
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DOI: https://doi.org/10.1038/nn.2704
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