title: The recurrent case for the Renshaw cell.
abstract: Although Renshaw cells (RCs) were discovered over half a century ago, their precise role in recurrent inhibition and ability to modulate motoneuron excitability have yet to be established. Indirect measurements of recurrent inhibition have suggested only a weak modulatory effect but are limited by the lack of observed motoneuron responses to inputs from single RCs. Here we present dual recordings between connected RC-motoneuron pairs, performed on mouse spinal cord. Motoneuron responses demonstrated that Renshaw synapses elicit large inhibitory conductances and show short-term potentiation. Anatomical reconstruction, combined with a novel method of quantal analysis, showed that the strong inhibitory input from RCs results from the large number of synaptic contacts that they make onto individual motoneurons. We used the NEURON simulation environment to construct realistic electrotonic models, which showed that inhibitory conductances from Renshaw inputs exert considerable shunting effects in motoneurons and reduce the frequency of spikes generated by excitatory inputs. This was confirmed experimentally by showing that excitation of a single RC or selective activation of the recurrent inhibitory pathway to generate equivalent inhibitory conductances both suppress motoneuron firing. We conclude that recurrent inhibition is remarkably effective, in that a single action potential from one RC is sufficient to silence a motoneuron. Although our results may differ from previous indirect observations, they underline a need for a reevaluation of the role that RCs perform in one of the first neuronal circuits to be discovered.
authors.affiliation: UCL Department of Neuroscience, Physiology and Pharmacology, London, WC1E 6BT, United Kingdom.
authors.forename: Gardave S
authors.initials: GS
authors.lastname: Bhumbra
authors.affiliation: Spinal Cord Group, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, United Kingdom, and.
authors.forename: B Anne
authors.identifier: http://orcid.org/0000-0002-1819-630X
authors.initials: BA
authors.lastname: Bannatyne
authors.affiliation: Hokkaido University, Department of Anatomy and Embryology, Sapporo, 060-8638, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Spinal Cord Group, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, United Kingdom, and.
authors.forename: Andrew J
authors.identifier: http://orcid.org/0000-0002-3007-6749
authors.initials: AJ
authors.lastname: Todd
authors.affiliation: Spinal Cord Group, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, United Kingdom, and m.beato@ucl.ac.uk david.maxwell@glasgow.ac.uk.
authors.forename: David J
authors.initials: DJ
authors.lastname: Maxwell
authors.affiliation: UCL Department of Neuroscience, Physiology and Pharmacology, London, WC1E 6BT, United Kingdom, m.beato@ucl.ac.uk david.maxwell@glasgow.ac.uk.
authors.forename: Marco
authors.identifier: http://orcid.org/0000-0002-7283-8318
authors.initials: M
authors.lastname: Beato
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D005260:Female; D007395:Interneurons / Q000166:cytology / Q000502:physiology*; D008297:Male; D051379:Mice; D008959:Models, Neurological; D009046:Motor Neurons / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology
keywords: feedback inhibition; motoneuron; quantal analysis; spinal cord