title: Synaptic Connectivity between Renshaw Cells and Motoneurons in the Recurrent Inhibitory Circuit of the Spinal Cord.
abstract: Renshaw cells represent a fundamental component of one of the first discovered neuronal circuits, but their function in motor control has not been established. They are the only central neurons that receive collateral projections from motor outputs, yet the efficacy of the excitatory synapses from single and converging motoneurons remains unknown. Here we present the results of dual whole-cell recordings from identified, synaptically connected Renshaw cell-motoneuron pairs in the mouse lumbar spinal cord. The responses from single Renshaw cells demonstrate that motoneuron synapses elicit large excitatory conductances with few or no failures. We show that the strong excitatory input from motoneurons results from a high probability of neurotransmitter release onto multiple postsynaptic contacts. Dual current-clamp recordings confirm that single motoneuron inputs were sufficient to depolarize the Renshaw cell beyond threshold for firing. Reciprocal connectivity was observed in approximately one-third of the paired recordings tested. Ventral root stimulation was used to evoke currents from Renshaw cells or motoneurons to characterize responses of single neurons to the activation of their corresponding presynaptic cell populations. Excitatory or inhibitory synaptic inputs in the recurrent inhibitory loop induced substantial effects on the excitability of respective postsynaptic cells. Quantal analysis estimates showed a large number of converging inputs from presynaptic motoneuron and Renshaw cell populations. The combination of considerable synaptic efficacy and extensive connectivity within the recurrent circuitry indicates a role of Renshaw cells in modulating motor outputs that may be considerably more important than has been previously supposed.
  
  
  CONCLUSIONS
  We have recently shown that Renshaw cells mediate powerful shunt inhibition on motoneuron excitability. Here we complete a quantitative description of the recurrent circuit using recordings of excitatory synapses between identified motoneuron and Renshaw cell pairs. We show that the excitation is highly effective as a result of a high probability of neurotransmitter release onto multiple release sites and that efficient neurotransmission is maintained at physiologically relevant firing rates in motoneurons. Our results also show that both excitatory and inhibitory connections exhibit considerable convergence of inputs. Because evaluation of the determinants of synaptic strength and the extent of connectivity constitute fundamental parameters affecting the operation of the recurrent circuit, our findings are critical for informing any future models of motor control.
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, United Kingdom.
authors.forename: Niall J
authors.identifier: http://orcid.org/0000-0001-6377-6373
authors.initials: NJ
authors.lastname: Moore
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, United Kingdom.
authors.forename: Gardave S
authors.initials: GS
authors.lastname: Bhumbra
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, United Kingdom.
authors.forename: Joshua D
authors.identifier: http://orcid.org/0000-0003-2015-363X
authors.initials: JD
authors.lastname: Foster
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, United Kingdom m.beato@ucl.ac.uk.
authors.forename: Marco
authors.identifier: http://orcid.org/0000-0002-7283-8318
authors.initials: M
authors.lastname: Beato
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D002118:Calcium / Q000378:metabolism; D004558:Electric Stimulation; D005260:Female; D050487:Glycine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology; D018408:Patch-Clamp Techniques; D066293:Renshaw Cells / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology*; D013569:Synapses / Q000502:physiology*; D055366:Synaptic Potentials / Q000502:physiology*
chemical_list: D050487:Glycine Plasma Membrane Transport Proteins; C493270:Slc6a5 protein, mouse; D002118:Calcium
keywords: Renshaw cell; motoneuron; quantal analysis; recurrent inhibition