Spinal Interneurons as Gatekeepers to Neuroplasticity after Injury or Disease

Zholudeva, Lyandysha V.; Abraira, Victoria E.; Satkunendrarajah, Kajana; McDevitt, Todd C.; Goulding, Martyn; Magnuson, David S.K.; Lane, Megan

doi:10.1523/jneurosci.1654-20.2020

Cited by 53 publications

(58 citation statements)

References 149 publications

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“…They integrate descending motor commands and sensory input from primary afferent fibers to modulate motor neuron activity and motor output [88,89]. There are diverse subpopulations of segmental spinal interneurons, many of which have been discovered in the context of understanding the neural control of locomotion and have been reviewed extensively elsewhere [90][91][92][93][94][95][96][97][98][99]. Long projecting propriospinal interneurons that connect cervical and lumbar enlargement are also important for interlimb coordination, especially during locomotion [100].…”

Section: Plasticity In Spared Descending Systemsmentioning

confidence: 99%

“…Interneurons in the cervical cord are involved in many tasks, such as breathing, locomotion, and reach-to-grasp [97,[105][106][107][108]. An example of propriospinal interneurons involved in the reach are the V2a interneurons, which relay information between motoneurons and the cerebellum to provide an 'internal feedback loop' [109].…”

Section: Plasticity In Spared Descending Systemsmentioning

confidence: 99%

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Plasticity in Cervical Motor Circuits following Spinal Cord Injury and Rehabilitation

Walker

Detloff

2021

Biology

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Neuroplasticity is a robust mechanism by which the central nervous system attempts to adapt to a structural or chemical disruption of functional connections between neurons. Mechanical damage from spinal cord injury potentiates via neuroinflammation and can cause aberrant changes in neural circuitry known as maladaptive plasticity. Together, these alterations greatly diminish function and quality of life. This review discusses contemporary efforts to harness neuroplasticity through rehabilitation and neuromodulation to restore function with a focus on motor recovery following cervical spinal cord injury. Background information on the general mechanisms of plasticity and long-term potentiation of the nervous system, most well studied in the learning and memory fields, will be reviewed. Spontaneous plasticity of the nervous system, both maladaptive and during natural recovery following spinal cord injury is outlined to provide a baseline from which rehabilitation builds. Previous research has focused on the impact of descending motor commands in driving spinal plasticity. However, this review focuses on the influence of physical therapy and primary afferent input and interneuron modulation in driving plasticity within the spinal cord. Finally, future directions into previously untargeted primary afferent populations are presented.

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Section: Plasticity In Spared Descending Systemsmentioning

confidence: 99%

Section: Plasticity In Spared Descending Systemsmentioning

confidence: 99%

Plasticity in Cervical Motor Circuits following Spinal Cord Injury and Rehabilitation

Walker

Detloff

2021

Biology

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“…In contrast, in eleven brain regions, notably the gigantocellular reticular nucleus, the red nucleus, the pedunculopontine nucleus, and the pontine central grey, regression slopes differed significantly from zero with R values that varied between 0.75 and 0.93 at different timepoints. Interestingly, the number of spared propriospinal neurons in cervical spinal cord, counted in cleared tissue between C2 and C6, also correlated well with functional recovery, highlighting the potential importance of cervical neurons as a supralumbar control center (R=0.83, slope<0 p=.0018, simple linear regression) ( Supplemental Figure 8 ) (Zholudeva et al, 2021). Overall, these data support the utility of whole-brain imaging and quantification to partially explain variability in functional outcomes after spinal injury.…”

Section: Resultsmentioning

confidence: 94%

Brain-wide analysis of the supraspinal connectome reveals anatomical correlates to functional recovery after spinal injury

Wang¹,

Romanski²,

Mehra³

et al. 2021

Preprint

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The supraspinal connectome is essential for normal behavior and homeostasis and consists of a wide range of sensory, motor, and autonomic projections from brain to spinal cord. Extensive work spanning a century has largely mapped the cell bodies of origin, yet their broad distribution and complex spatial relationships present significant challenges to the dissemination and application of this knowledge. Fields that study disruptions of supraspinal projections, for example spinal cord injury, have focused mostly on a handful of major populations that carry motor commands, with only limited consideration of dozens more that provide autonomic or crucial motor modulation. More comprehensive information is essential to understand the functional consequences of different injuries and to better evaluate the efficacy of treatments. Using viral retrograde labeling, 3D imaging, and registration to standard neuro-anatomical atlases we now provide a platform to profile the entire supraspinal connectome by rapidly visualizing and quantifying tens of thousands of supraspinal neurons, each assigned to more than 60 identified regions and nuclei throughout the brains of adult mice. We then use this tool to compare the lumbar versus cervically-projecting connectomes, to profile brain-wide the sensitivity of supraspinal populations to graded spinal injuries, and to correlate locomotor recovery with connectome measurements. To share these insights in an intuitive manner, we present an interactive web-based resource, which aims to spur progress by broadening understanding and analyses of essential but understudied supraspinal populations.

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“…These changes can also refine and prune synaptic connections and promote the recruitment of other neurons (e.g., spinal interneurons) into the neural network ( Rank et al, 2015 ; Sandhu et al, 2015 ; Streeter et al, 2017 ). Spinal interneurons (SpINs) are a vital component of neuroplasticity ( Zholudeva and Lane, 2018 ; Zholudeva et al, 2021 ), that can change their pattern of activity and are reported to alter their connectivity to contribute to novel anatomical pathways. Most importantly, this neuroplastic potential can be therapeutically driven by either electrical stimulation or ABTs ( Harkema, 2008 ; van den Brand et al, 2012 ; Houle and Cote, 2013 ).…”

Section: Methods To Enhance Plasticitymentioning

confidence: 99%

Respiratory Training and Plasticity After Cervical Spinal Cord Injury

Randelman

Zholudeva

Vinit

et al. 2021

Front. Cell. Neurosci.

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While spinal cord injuries (SCIs) result in a vast array of functional deficits, many of which are life threatening, the majority of SCIs are anatomically incomplete. Spared neural pathways contribute to functional and anatomical neuroplasticity that can occur spontaneously, or can be harnessed using rehabilitative, electrophysiological, or pharmacological strategies. With a focus on respiratory networks that are affected by cervical level SCI, the present review summarizes how non-invasive respiratory treatments can be used to harness this neuroplastic potential and enhance long-term recovery. Specific attention is given to “respiratory training” strategies currently used clinically (e.g., strength training) and those being developed through pre-clinical and early clinical testing [e.g., intermittent chemical stimulation via altering inhaled oxygen (hypoxia) or carbon dioxide stimulation]. Consideration is also given to the effect of training on non-respiratory (e.g., locomotor) networks. This review highlights advances in this area of pre-clinical and translational research, with insight into future directions for enhancing plasticity and improving functional outcomes after SCI.

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Spinal Interneurons as Gatekeepers to Neuroplasticity after Injury or Disease

Cited by 53 publications

References 149 publications

Plasticity in Cervical Motor Circuits following Spinal Cord Injury and Rehabilitation

Plasticity in Cervical Motor Circuits following Spinal Cord Injury and Rehabilitation

Brain-wide analysis of the supraspinal connectome reveals anatomical correlates to functional recovery after spinal injury

Respiratory Training and Plasticity After Cervical Spinal Cord Injury

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