A decerebrate adult mouse model for examining the sensorimotor control of locomotion.

As wild-type and genetically modified mice are progressively becoming the predominant models for studying locomotor physiology, the technical ability to record sensory and motor components from adult mice, in vivo, are expected to contribute to a better understanding of sensorimotor spinal cord networks. Here, specific technical and surgical details are presented on how to produce an adult decerebrate mouse preparation that can reliably produce sustained bouts of stepping, in vivo, in the absence of anesthetic drugs. Data are presented demonstrating the ability of this preparation to produce stepping during treadmill locomotion, adaptability in its responses to changes in the treadmill speed, and left-right alternation. Furthermore, intracellular recordings from motoneurons and interneurons in the spinal cord are presented from preparations where muscle activity was blocked. Intraaxonal recordings are also presented demonstrating that individual afferents can be recorded using this preparation. These data demonstrate that the adult decerebrate mouse is a tractable preparation for the study of sensorimotor systems.

[1]  S. Edgley,et al.  A short‐latency crossed pathway from cutaneous afferents to rat hindlimb motoneurones. , 1989, The Journal of physiology.

[2]  S. Schäfer,et al.  The period of latency before a muscle receptor generates an action potential as a response to a muscle stretch , 1999, Brain Research.

[3]  C. Heckman,et al.  Altered postnatal maturation of electrical properties in spinal motoneurons in a mouse model of amyotrophic lateral sclerosis , 2011, The Journal of physiology.

[4]  Y. Aikawa,et al.  Manual acupuncture needle stimulation of the rat hindlimb activates groups I, II, III and IV single afferent nerve fibers in the dorsal spinal roots. , 2005, The Japanese journal of physiology.

[5]  Erin V. L. Vasudevan,et al.  Younger Is Not Always Better: Development of Locomotor Adaptation from Childhood to Adulthood , 2011, The Journal of Neuroscience.

[6]  S. Grillner The motor infrastructure: from ion channels to neuronal networks , 2003, Nature Reviews Neuroscience.

[7]  T. Bedford,et al.  A model of dynamic exercise: the decerebrate rat locomotor preparation. , 1992, Journal of applied physiology.

[8]  K. Kanda,et al.  Age‐related physiological and morphological changes of muscle spindles in rats , 2007, The Journal of physiology.

[9]  J. Dostrovsky,et al.  Central sensitization of nociceptive neurons in rat medullary dorsal horn involves purinergic P2X7 receptors , 2011, Neuroscience.

[10]  J. Eccles,et al.  Spinal cord potentials generated by volleys in the large muscle afferents , 1954, The Journal of physiology.

[11]  E. Eldred,et al.  Static stretch sensitivity of Ia and II afferents in the cat's gastrocnemius , 1982, Pflügers Archiv.

[12]  C. Woolf,et al.  Central sensitization: a generator of pain hypersensitivity by central neural plasticity. , 2009, The journal of pain : official journal of the American Pain Society.

[13]  K. Koketsu,et al.  Cholinergic and inhibitory synapses in a pathway from motor‐axon collaterals to motoneurones , 1954, The Journal of physiology.

[14]  P. Matthews,et al.  The response of de‐efferented muscle spindle receptors to stretching at different velocities , 1963, The Journal of physiology.

[15]  P. Andersen,et al.  A novel SOD1 splice site mutation associated with familial ALS revealed by SOD activity analysis. , 2010, Human molecular genetics.

[16]  M. Fitzgerald Cutaneous primary afferent properties in the hind limb of the neonatal rat. , 1987 .

[17]  J. Nielsen,et al.  Reciprocal Ia inhibition contributes to motoneuronal hyperpolarisation during the inactive phase of locomotion and scratching in the cat , 2011, The Journal of physiology.

[18]  Physiological properties of primary sensory neurons appropriately and inappropriately innervating skin in the adult rat. , 1991, Journal of neurophysiology.

[19]  F. J. Alvarez,et al.  The continuing case for the Renshaw cell , 2007, The Journal of physiology.

[20]  J. Stamford Descending control of pain. , 1995, British journal of anaesthesia.

[21]  M D Binder,et al.  Analysis of effective synaptic currents generated by homonymous Ia afferent fibers in motoneurons of the cat. , 1988, Journal of neurophysiology.

[22]  S. Rossignol,et al.  Contralateral hindlimb responses to cutaneous stimulation during locomotion in high decerebrate cats , 1981, Brain Research.

[23]  Amy J Bastian,et al.  Split-Belt Treadmill Training Poststroke: A Case Study , 2010, Journal of neurologic physical therapy : JNPT.

[24]  L. Kurland,et al.  ALS in Rochester, Minnesota, 1925–1977 , 1980, Neurology.

[25]  J. Nielsen,et al.  Intrinsic properties of mouse lumbar motoneurons revealed by intracellular recording in vivo. , 2010, Journal of neurophysiology.

[26]  B. Renshaw Central effects of centripetal impulses in axons of spinal ventral roots. , 1946, Journal of neurophysiology.

[27]  Jaynie F. Yang,et al.  Training of Walking Skills Overground and on the Treadmill: Case Series on Individuals With Incomplete Spinal Cord Injury , 2009, Physical Therapy.

[28]  R. Burke Motor Units: Anatomy, Physiology, and Functional Organization , 1981 .

[29]  B. Schmidt,et al.  Regional distribution of the locomotor pattern-generating network in the neonatal rat spinal cord. , 1997, Journal of neurophysiology.

[30]  J. Eccles,et al.  The central action of antidromic impulses in motor nerve fibres , 2004, Pflüger's Archiv für die gesamte Physiologie des Menschen und der Tiere.

[31]  M. Zimmermann,et al.  Pathobiology of neuropathic pain. , 2001, European journal of pharmacology.

[32]  D. Kernell,et al.  The “fastness” of rat motoneurones: time-course of afterhyperpolarization in relation to axonal conduction velocity and muscle unit contractile speed , 1990, Pflügers Archiv.

[33]  D. Burke,et al.  Monosynaptic and oligosynaptic contributions to human ankle jerk and H-reflex. , 1984, Journal of neurophysiology.

[34]  F. Clarac,et al.  Perinatal development of lumbar motoneurons and their inputs in the rat , 2000, Brain Research Bulletin.

[35]  J. Iles,et al.  Fictive locomotion in the adult decerebrate rat , 1996, Experimental Brain Research.

[36]  R. Gracely,et al.  Stability and reliability of detection thresholds for human A-Beta and A-delta sensory afferents determined by cutaneous electrical stimulation. , 2003, Journal of pain and symptom management.

[37]  A. Eisen,et al.  Duration of amyotrophic lateral sclerosis is age dependent , 1993, Muscle & nerve.

[38]  S. Nakanishi,et al.  Diversification of intrinsic motoneuron electrical properties during normal development and botulinum toxin-induced muscle paralysis in early postnatal mice. , 2010, Journal of neurophysiology.

[39]  C. Hulsebosch,et al.  Neuronal Hyperexcitability: A Substrate for Central Neuropathic Pain After Spinal Cord Injury , 2011, Current pain and headache reports.

[40]  Jonathan R Wolpaw,et al.  An in vitro protocol for recording from spinal motoneurons of adult rats. , 2008, Journal of neurophysiology.

[41]  A. Ludolph,et al.  Amyotrophic lateral sclerosis. , 2012, Current opinion in neurology.

[42]  H. Hultborn,et al.  Intrinsic properties of lumbar motor neurones in the adult G127insTGGG superoxide dismutase‐1 mutant mouse in vivo: evidence for increased persistent inward currents , 2010, Acta physiologica.

[43]  Ole Kiehn,et al.  Role of EphA4 and EphrinB3 in Local Neuronal Circuits That Control Walking , 2003, Science.

[44]  J. Eccles,et al.  Potential changes recorded inside primary afferent fibres within the spinal cord , 1959, The Journal of physiology.

[45]  J. Nielsen,et al.  Enhanced spinal excitation from ankle flexors to knee extensors during walking in stroke patients , 2010, Clinical Neurophysiology.

[46]  C. Heckman,et al.  Progressive Changes in Synaptic Inputs to Motoneurons in Adult Sacral Spinal Cord of a Mouse Model of Amyotrophic Lateral Sclerosis , 2009, The Journal of Neuroscience.

[47]  T. Brown The intrinsic factors in the act of progression in the mammal , 1911 .

[48]  K Kramer,et al.  Use of telemetry to record electrocardiogram and heart rate in freely moving mice. , 1993, Journal of pharmacological and toxicological methods.

[49]  R. Brownstone Beginning at the end: Repetitive firing properties in the final common pathway , 2006, Progress in Neurobiology.

[50]  H. Hultborn,et al.  A prolongation of the postspike afterhyperpolarization following spike trains can partly explain the lower firing rates at derecruitment than those at recruitment. , 2009, Journal of neurophysiology.

[51]  O Kiehn,et al.  Distribution of Networks Generating and Coordinating Locomotor Activity in the Neonatal Rat Spinal Cord In Vitro: A Lesion Study , 1996, The Journal of Neuroscience.

[52]  K. G. Pearson,et al.  A new electrode configuration for recording electromyographic activity in behaving mice , 2005, Journal of Neuroscience Methods.

[53]  M. Pinter,et al.  Regulation of Motoneuron Excitability via Motor Endplate Acetylcholine Receptor Activation , 2005, The Journal of Neuroscience.

[54]  Y. Datian,et al.  Cutaneous Electrical Stimulation of Mid-frequency on Acupiont Affects the Electrogastrogram , 2005, 2005 IEEE Engineering in Medicine and Biology 27th Annual Conference.

[55]  J. Prather,et al.  Central Suppression of Regenerated Proprioceptive Afferents , 2005, The Journal of Neuroscience.

[56]  A study of synaptic connection between low threshold afferent fibres in common peroneal nerve and motoneurones in human tibialis anterior , 2008, Experimental Brain Research.

[57]  R. North,et al.  Synaptic potentials in rat locus coeruleus neurones. , 1988, The Journal of physiology.

[58]  T. Nichols,et al.  Movement reduces the dynamic response of muscle spindle afferents and motoneuron synaptic potentials in rat. , 2004, Journal of neurophysiology.

[59]  B. Hyman,et al.  Apolipoprotein E epsilon 4 allele is not associated with earlier age at onset in amyotrophic lateral sclerosis. , 1995, Annals of neurology.

[60]  A. Herz,et al.  Endogenous opioid peptides in the descending control of nociceptive responses of spinal dorsal horn neurons. , 1988, Progress in brain research.

[61]  S. Rutkowski,et al.  Electrical Perceptual Threshold Testing: A Validation Study , 2009, The journal of spinal cord medicine.

[62]  S. Rossignol,et al.  The locomotion of the low spinal cat. II. Interlimb coordination. , 1980, Acta physiologica Scandinavica.

[63]  P. Whelan CONTROL OF LOCOMOTION IN THE DECEREBRATE CAT , 1996, Progress in Neurobiology.

[64]  Daniel Zytnicki,et al.  Fast Kinetics, High-Frequency Oscillations, and Subprimary Firing Range in Adult Mouse Spinal Motoneurons , 2009, The Journal of Neuroscience.

[65]  Y Mor,et al.  Analysis of rhythmic patterns produced by spinal neural networks. , 2007, Journal of neurophysiology.

[66]  M. Fung,et al.  Involvement of pontile NMDA receptors in inspiratory termination in rat. , 1994, Respiration physiology.

[67]  Arick G. Auyang,et al.  Whole limb kinematics are preferentially conserved over individual joint kinematics after peripheral nerve injury , 2009, Journal of Experimental Biology.

[68]  C C Hunt,et al.  Proportion of fatigue‐resistant motor units in hindlimb muscles of cat and their relation to axonal conduction velocity. , 1988, The Journal of physiology.

[69]  Kenneth A. Clarke,et al.  Swing time changes contribute to stride time adjustment in the walking rat , 1991, Physiology & Behavior.

[70]  A. Lev-Tov,et al.  Localization of the spinal network associated with generation of hindlimb locomotion in the neonatal rat and organization of its transverse coupling system. , 1997, Journal of neurophysiology.

[71]  O. Kiehn,et al.  Spatiotemporal characteristics of 5-HT and dopamine-induced rhythmic hindlimb activity in the in vitro neonatal rat. , 1996, Journal of neurophysiology.

[72]  S. Edgley,et al.  Crossed reflex actions from group II muscle afferents in the lumbar spinal cord of the anaesthetized cat. , 1991, Journal of Physiology.

[73]  N. Petersen,et al.  Flexor reflex afferents reset the step cycle during fictive locomotion in the cat , 1998, Experimental Brain Research.

[74]  Robert H. Brown,et al.  Apolipoprotein E ϵ4 allele is not associated with earlier age at onset in amyotrophic lateral sclerosis , 1995 .

[75]  D. Reisman,et al.  Locomotor adaptation on a split-belt treadmill can improve walking symmetry post-stroke. , 2007, Brain : a journal of neurology.

[76]  E. Silbergeld,et al.  Abnormal locomotion in rats after bilateral intrastriatal injection of kainic acid. , 1979, Life sciences.

[77]  M. Taussig The Nervous System , 1991 .

[78]  Jonathan T. Brown,et al.  Washington, DC: Society for Neuroscience, 2011 , 2011 .

[79]  C. Heckman,et al.  Hyperexcitability of cultured spinal motoneurons from presymptomatic ALS mice. , 2004, Journal of neurophysiology.

[80]  C. Sherrington Integrative Action of the Nervous System , 1907 .

[81]  M. Pinter,et al.  Enhanced Transmission at a Spinal Synapse Triggered In Vivo by an Injury Signal Independent of Altered Synaptic Activity , 2007, The Journal of Neuroscience.

[82]  Ole Kiehn,et al.  Activity of Renshaw Cells during Locomotor-Like Rhythmic Activity in the Isolated Spinal Cord of Neonatal Mice , 2006, The Journal of Neuroscience.

[83]  R. Harris-Warrick,et al.  Long-duration perforated patch recordings from spinal interneurons of adult mice. , 2011, Journal of neurophysiology.

[84]  Bruce Walmsley,et al.  An in vivo pharmacological study of single group Ia fibre contacts with motoneurones in the cat spinal cord. , 1994, The Journal of physiology.

[85]  A. Lundberg Multisensory control of spinal reflex pathways. , 1979, Progress in brain research.