Descending propriospinal neurons mediate restoration of locomotor function following spinal cord injury

Benthall, Katelyn N.; Hough, Ryan A.; McClellan, Andrew D.

doi:10.1152/jn.00544.2016

Cited by 19 publications

(16 citation statements)

References 74 publications

(113 reference statements)

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“…Finally, following incorporation of the ML in the model, right-left phase values changed very little (Figure 10D4 ), as also shown experimentally (Figure 3C4 ). This basic phase oscillator model mimicked many of the neurobiological results for the present study, and has mimicked most of the neurobiological results for five previous studies: McClellan and Jang ( 1993 ); Hagevik and McClellan ( 1994 ); McClellan and Hagevik ( 1997 , 1999 ); Benthall et al ( 2017 ).…”

Section: Discussionsupporting

confidence: 85%

Elimination of Left-Right Reciprocal Coupling in the Adult Lamprey Spinal Cord Abolishes the Generation of Locomotor Activity

Messina

Paul

Hargis

et al. 2017

Front. Neural Circuits

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The contribution of left-right reciprocal coupling between spinal locomotor networks to the generation of locomotor activity was tested in adult lampreys. Muscle recordings were made from normal animals as well as from experimental animals with rostral midline (ML) spinal lesions (~13%→35% body length, BL), before and after spinal transections (T) at 35% BL. Importantly, in the present study actual locomotor movements and muscle burst activity, as well as other motor activity, were initiated in whole animals by descending brain-spinal pathways in response to sensory stimulation of the anterior head. For experimental animals with ML spinal lesions, sensory stimulation could elicit well-coordinated locomotor muscle burst activity, but with some significant differences in the parameters of locomotor activity compared to those for normal animals. Computer models representing normal animals or experimental animals with ML spinal lesions could mimic many of the differences in locomotor activity. For experimental animals with ML and T spinal lesions, right and left rostral hemi-spinal cords, disconnected from intact caudal cord, usually produced tonic or unpatterned muscle activity. Hemi-spinal cords sometimes generated spontaneous or sensory-evoked relatively high frequency “burstlet” activity that probably is analogous to the previously described in vitro “fast rhythm”, which is thought to represent lamprey locomotor activity. However, “burstlet” activity in the present study had parameters and features that were very different than those for lamprey locomotor activity: average frequencies were ~25 Hz, but individual frequencies could be >50 Hz; burst proportions (BPs) often varied with cycled time; “burstlet” activity usually was not accompanied by a rostrocaudal phase lag; and following ML spinal lesions alone, “burstlet” activity could occur in the presence or absence of swimming burst activity, suggesting the two were generated by different mechanisms. In summary, for adult lampreys, left and right hemi-spinal cords did not generate rhythmic locomotor activity in response to descending inputs from the brain, suggesting that left-right reciprocal coupling of spinal locomotor networks contributes to both phase control and rhythmogenesis. In addition, the present study indicates that extreme caution should be exercised when testing the operation of spinal locomotor networks using artificial activation of isolated or reduced nervous system preparations.

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Section: Discussionsupporting

confidence: 85%

Elimination of Left-Right Reciprocal Coupling in the Adult Lamprey Spinal Cord Abolishes the Generation of Locomotor Activity

Messina

Paul

Hargis

et al. 2017

Front. Neural Circuits

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“…Additionally, collateral sprouting of spared UMNs and regrowth of local propriospinal fibers traversing the site of injury have each been shown in experimental injury in rodents and lampreys (52)(53)(54)(55). These mechanisms serve to produce novel, multisynaptic pathways, and reestablish the connections between UMNs and LMNs with associated improvements in motor function (39,52).…”

Section: Plasticity Of Locomotor Systems After Scimentioning

confidence: 98%

Ambulation in Dogs With Absent Pain Perception After Acute Thoracolumbar Spinal Cord Injury

2020

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Acute thoracolumbar spinal cord injury (SCI) is common in dogs frequently secondary to intervertebral disc herniation. Following severe injury, some dogs never regain sensory function to the pelvic limbs or tail and are designated chronically "deep pain negative." Despite this, a subset of these dogs develop spontaneous motor recovery over time including some that recover sufficient function in their pelvic limbs to walk independently without assistance or weight support. This type of ambulation is commonly known as "spinal walking" and can take up to a year or more to develop. This review provides a comparative overview of locomotion and explores the physiology of locomotor recovery after severe SCI in dogs. We discuss the mechanisms by which post-injury plasticity and coordination between circuitry contained within the spinal cord, peripheral sensory feedback, and residual or recovered supraspinal connections might combine to underpin spinal walking. The clinical characteristics of spinal walking are outlined including what is known about the role of patient or injury features such as lesion location, timeframe post-injury, body size, and spasticity. The relationship between the emergence of spinal walking and electrodiagnostic and magnetic resonance imaging findings are also discussed. Finally, we review possible ways to predict or facilitate recovery of walking in chronically deep pain negative dogs. Improved understanding of the mechanisms of gait generation and plasticity of the surviving tissue after injury might pave the way for further treatment options and enhanced outcomes in severely injured dogs.

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“…Propriospinal interneurons in humans may also play an important role in motor recovery after spinal cord injury as PINs were identified in animals as key players to form relays or detours in the injured spinal cord and thus are critical in promoting functional recovery ( Bareyre et al, 2004 ; Vavrek et al, 2006 ; Courtine et al, 2008 ; Flynn et al, 2011 ; Benthall et al, 2017 ) by being more resistant to injury and degeneration ( Conta and Stelzner, 2004 ). The plastic potential of PINs and contribution to recovery in humans is supported by evidence of reemergence in interlimb reflexes 6 or more months after a cervical spinal cord injury ( Calancie et al, 2005 ).…”

Section: Classification Of Spinal Interneuronsmentioning

confidence: 99%

Spinal Control of Locomotion: Individual Neurons, Their Circuits and Functions

2018

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Systematic research on the physiological and anatomical characteristics of spinal cord interneurons along with their functional output has evolved for more than one century. Despite significant progress in our understanding of these networks and their role in generating and modulating movement, it has remained a challenge to elucidate the properties of the locomotor rhythm across species. Neurophysiological experimental evidence indicates similarities in the function of interneurons mediating afferent information regarding muscle stretch and loading, being affected by motor axon collaterals and those mediating presynaptic inhibition in animals and humans when their function is assessed at rest. However, significantly different muscle activation profiles are observed during locomotion across species. This difference may potentially be driven by a modified distribution of muscle afferents at multiple segmental levels in humans, resulting in an altered interaction between different classes of spinal interneurons. Further, different classes of spinal interneurons are likely activated or silent to some extent simultaneously in all species. Regardless of these limitations, continuous efforts on the function of spinal interneuronal circuits during mammalian locomotion will assist in delineating the neural mechanisms underlying locomotor control, and help develop novel targeted rehabilitation strategies in cases of impaired bipedal gait in humans. These rehabilitation strategies will include activity-based therapies and targeted neuromodulation of spinal interneuronal circuits via repetitive stimulation delivered to the brain and/or spinal cord.

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Descending propriospinal neurons mediate restoration of locomotor function following spinal cord injury

Cited by 19 publications

References 74 publications

Elimination of Left-Right Reciprocal Coupling in the Adult Lamprey Spinal Cord Abolishes the Generation of Locomotor Activity

Elimination of Left-Right Reciprocal Coupling in the Adult Lamprey Spinal Cord Abolishes the Generation of Locomotor Activity

Ambulation in Dogs With Absent Pain Perception After Acute Thoracolumbar Spinal Cord Injury

Spinal Control of Locomotion: Individual Neurons, Their Circuits and Functions

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