Recurrent excitation between motoneurones propagates across segments and is purely glutamatergic

Spinal motoneurones (Mns) constitute the final output for the execution of motor tasks. In addition to innervating muscles, Mns project excitatory collateral connections to Renshaw cells (RCs) and other Mns, but the latter have received little attention. We show that Mns receive strong synaptic input from other Mns throughout development and into maturity, with fast-type Mns systematically receiving greater recurrent excitation than slow-type Mns. Optical recordings show that activation of Mns in one spinal segment can propagate to adjacent segments even in the presence of intact recurrent inhibition. While it is known that transmission at the neuromuscular junction is purely cholinergic and RCs are excited through both acetylcholine and glutamate receptors, here we show that neurotransmission between Mns is purely glutamatergic, indicating that synaptic transmission systems are differentiated at different postsynaptic targets of Mns.

[1]  G. Horcholle-Bossavit,et al.  Direct excitatory interactions between spinal motoneurones of the cat. , 1977, The Journal of physiology.

[2]  S. Cullheim,et al.  Evidence for direct synaptic interconnections between cat spinal α-motoneurons via the recurrent axon collaterals: A morphological study using intracellular injection of horseradish peroxidase , 1977, Brain Research.

[3]  R. Coggeshall Law of separation of function of the spinal roots. , 1980, Physiological reviews.

[4]  Z. Jiang,et al.  Excitatory postsynaptic potentials evoked by ventral root stimulation in neonate rat motoneurons in vitro. , 1991, Journal of neurophysiology.

[5]  A. Roberts,et al.  Cholinergic and electrical synapses between synergistic spinal motoneurones in the Xenopus laevis embryo. , 1995, The Journal of physiology.

[6]  T. Ichinose,et al.  Recurrent excitation of motoneurons in the isolated spinal cord of newborn rats detected by whole-cell recording , 1998, Neuroscience Research.

[7]  G. G. Nagy,et al.  The expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in neurochemically defined axonal populations in the rat spinal cord with emphasis on the dorsal horn , 2003, The European journal of neuroscience.

[8]  R. Villalba,et al.  Vesicular glutamate transporters in the spinal cord, with special reference to sensory primary afferent synapses , 2004, The Journal of comparative neurology.

[9]  C. Legay,et al.  Expression of vesicular glutamate transporters, VGLUT1 and VGLUT2, in cholinergic spinal motoneurons , 2004, The European journal of neuroscience.

[10]  Giorgio A Ascoli,et al.  Developmental changes in spinal motoneuron dendrites in neonatal mice , 2005, The Journal of comparative neurology.

[11]  G. Dugué,et al.  Target-Dependent Use of Coreleased Inhibitory Transmitters at Central Synapses , 2005, The Journal of Neuroscience.

[12]  Y. Yanagawa,et al.  Mammalian motor neurons corelease glutamate and acetylcholine at central synapses. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[13]  Michael J. O'Donovan,et al.  Noncholinergic excitatory actions of motoneurons in the neonatal mammalian spinal cord. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Hanns Ulrich Zeilhofer,et al.  Glycinergic neurons expressing enhanced green fluorescent protein in bacterial artificial chromosome transgenic mice , 2005, The Journal of comparative neurology.

[15]  S. Hochman,et al.  Noradrenaline Unmasks Novel Self-Reinforcing Motor Circuits within the Mammalian Spinal Cord , 2006, The Journal of Neuroscience.

[16]  N. Spitzer,et al.  Activity-dependent neurotransmitter-receptor matching at the neuromuscular junction , 2007, Proceedings of the National Academy of Sciences.

[17]  D. McCrea,et al.  Organization of mammalian locomotor rhythm and pattern generation , 2008, Brain Research Reviews.

[18]  P. Ascher,et al.  Four Excitatory Postsynaptic Ionotropic Receptors Coactivated at the Motoneuron–Renshaw Cell Synapse , 2008, The Journal of Neuroscience.

[19]  E. Jankowska,et al.  Cholinergic terminals in the ventral horn of adult rat and cat: Evidence that glutamate is a cotransmitter at putative interneuron synapses but not at central synapses of motoneurons , 2009, Neuroscience.

[20]  Michael J. O'Donovan,et al.  Excitatory actions of ventral root stimulation during network activity generated by the disinhibited neonatal mouse spinal cord. , 2009, Journal of neurophysiology.

[21]  O. Kiehn,et al.  Firing and Cellular Properties of V2a Interneurons in the Rodent Spinal Cord , 2010, The Journal of Neuroscience.

[22]  P. Ascher,et al.  Mechanisms Shaping the Slow Nicotinic Synaptic Current at the Motoneuron–Renshaw Cell Synapse , 2012, The Journal of Neuroscience.

[23]  Stefan R. Pulver,et al.  Ultra-sensitive fluorescent proteins for imaging neuronal activity , 2013, Nature.

[24]  F. J. Alvarez,et al.  Motor Axon Synapses on Renshaw Cells Contain Higher Levels of Aspartate than Glutamate , 2014, PloS one.

[25]  D. Zytnicki,et al.  Early intrinsic hyperexcitability does not contribute to motoneuron degeneration in amyotrophic lateral sclerosis , 2014, eLife.

[26]  Masahiko Watanabe,et al.  The Recurrent Case for the Renshaw Cell , 2014, The Journal of Neuroscience.

[27]  Gary S Bhumbra,et al.  Synaptic Connectivity between Renshaw Cells and Motoneurons in the Recurrent Inhibitory Circuit of the Spinal Cord , 2015, The Journal of Neuroscience.

[28]  Nathan C. Klapoetke,et al.  Transgenic Mice for Intersectional Targeting of Neural Sensors and Effectors with High Specificity and Performance , 2015, Neuron.

[29]  O. Kiehn Decoding the organization of spinal circuits that control locomotion , 2016, Nature Reviews Neuroscience.

[30]  Abdeljabbar El Manira,et al.  Motor neurons control locomotor circuit function retrogradely via gap junctions , 2016, Nature.

[31]  Michael J. O'Donovan,et al.  Motoneurons regulate the central pattern generator during drug-induced locomotor-like activity in the neonatal mouse , 2017, eLife.

[32]  Segregation of glutamatergic and cholinergic transmission at the mixed motoneuron Renshaw cell synapse , 2017, Scientific Reports.