scholarly journals Corticospinal circuit remodeling after central nervous system injury is dependent on neuronal activity

2019 ◽  
Vol 216 (11) ◽  
pp. 2503-2514 ◽  
Author(s):  
Peter M. Bradley ◽  
Carmen K. Denecke ◽  
Almir Aljovic ◽  
Anja Schmalz ◽  
Martin Kerschensteiner ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Target Selection ◽  
Neuronal Firing ◽  
Neuron Activity ◽  
Cortical Projection ◽  
Relay Neuron ◽  
Cord Injury ◽  
Activity Dependent ◽  
Relay Neurons

The remodeling of supraspinal axonal circuits mediates functional recovery after spinal cord injury. This process critically depends on the selection of appropriate synaptic connections between cortical projection and spinal relay neurons. To unravel the principles that guide this target selection, we used genetic and chemogenetic tools to modulate NMDA receptor (NMDAR) integrity and function, CREB-mediated transcription, and neuronal firing of relay neurons during injury-induced corticospinal remodeling. We show that NMDAR signaling and CREB-mediated transcription maintain nascent corticospinal tract (CST)–relay neuron contacts. These activity-dependent signals act during a defined period of circuit remodeling and do not affect mature or uninjured circuits. Furthermore, chemogenetic modulation of relay neuron activity reveals that the regrowing CST axons select their postsynaptic partners in a competitive manner and that preventing such activity-dependent shaping of corticospinal circuits limits motor recovery after spinal cord injury.

scholarly journals Effects of a Contusive Spinal Cord Injury on Spinal Motor Neuron Activity and Conduction Time in Rats

2020 ◽  
Author(s):  
Jordan A. Borrell ◽  
Dora Krizsan-Agbas ◽  
Randolph J. Nudo ◽  
Shawn B. Frost
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spike Activity ◽  
Short Latency ◽  
Neuron Activity ◽  
Emg Activity ◽  
Conduction Time ◽  
Dorsal Midline ◽  
Cord Injury ◽  
Contusion Injury

AbstractObjectiveThe purpose of this study was to determine the effects of spinal cord injury (SCI) on spike activity evoked in the hindlimb spinal cord of the rat from cortical electrical stimulation.ApproachAdult, male, Sprague Dawley rats were randomly assigned to a Healthy or SCI group. SCI rats were given a 175 kDyn dorsal midline contusion injury at the level of the T8 vertebrae. At four weeks post-SCI, intracortical microstimulation (ICMS) was delivered at several sites in the hindlimb motor cortex of anesthetized rats, and evoked neural activity was recorded from corresponding sites throughout the dorsoventral depths of the spinal cord and EMG activity from hindlimb muscles.Main resultsIn healthy rats, post-ICMS spike histograms showed reliable, evoked spike activity during a short-latency epoch 10-12 ms after the initiation of the ICMS pulse train (short). Longer latency spikes occurred between ~20-60 ms, generally following a Gaussian distribution, rising above baseline at time LON, followed by a peak response (Lp), and then falling below baseline at time LOFF. EMG responses occurred between LON and Lp (25-27 ms). In SCI rats, short-latency responses were still present, long-latency responses were disrupted or eliminated, and EMG responses were never evoked. The retention of the short-latency responses indicates that spared descending spinal fibers, most likely via the cortico-reticulospinal pathway, can still depolarize spinal cord motor neurons after a dorsal midline contusion injury.SignificanceThis study provides novel insights into the role of alternate pathways for voluntary control of hindlimb movements after SCI that disrupts the corticospinal tract in the rat.

An investigation into the potential for activity-dependent regeneration of the rubrospinal tract after spinal cord injury

2005 ◽  
Vol 22 (12) ◽  
pp. 3025-3035 ◽  
Author(s):  
Philip J. Harvey ◽  
Joey Grochmal ◽  
Wolfram Tetzlaff ◽  
Tessa Gordon ◽  
David J. Bennett
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rubrospinal Tract ◽  
Cord Injury ◽  
Activity Dependent

The Beneficial Effects of Treadmill Step Training on Activity-Dependent Synaptic and Cellular Plasticity Markers After Complete Spinal Cord Injury

2011 ◽  
Vol 36 (6) ◽  
pp. 1046-1055 ◽  
Author(s):  
Jocemar Ilha ◽  
Lígia A. Centenaro ◽  
Núbia Broetto Cunha ◽  
Daniela F. de Souza ◽  
Mariane Jaeger ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cellular Plasticity ◽  
Beneficial Effects ◽  
Cord Injury ◽  
Complete Spinal Cord Injury ◽  
Activity Dependent

scholarly journals Targeted, activity-dependent spinal stimulation produces long-lasting motor recovery in chronic cervical spinal cord injury

2015 ◽  
Vol 112 (39) ◽  
pp. 12193-12198 ◽  
Author(s):  
Jacob G. McPherson ◽  
Robert R. Miller ◽  
Steve I. Perlmutter
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neural Plasticity ◽  
Enhanced Recovery ◽  
Cervical Spinal Cord ◽  
Spike Timing ◽  
Neurological Injury ◽  
Partial Recovery ◽  
Cord Injury ◽  
Activity Dependent

Use-dependent movement therapies can lead to partial recovery of motor function after neurological injury. We attempted to improve recovery by developing a neuroprosthetic intervention that enhances movement therapy by directing spike timing-dependent plasticity in spared motor pathways. Using a recurrent neural–computer interface in rats with a cervical contusion of the spinal cord, we synchronized intraspinal microstimulation below the injury with the arrival of functionally related volitional motor commands signaled by muscle activity in the impaired forelimb. Stimulation was delivered during physical retraining of a forelimb behavior and throughout the day for 3 mo. Rats receiving this targeted, activity-dependent spinal stimulation (TADSS) exhibited markedly enhanced recovery compared with animals receiving targeted but open-loop spinal stimulation and rats receiving physical retraining alone. On a forelimb reach and grasp task, TADSS animals recovered 63% of their preinjury ability, more than two times the performance level achieved by the other therapy groups. Therapeutic gains were maintained for 3 additional wk without stimulation. The results suggest that activity-dependent spinal stimulation can induce neural plasticity that improves behavioral recovery after spinal cord injury.

scholarly journals Activity-Dependent Increase in Neurotrophic Factors Is Associated with an Enhanced Modulation of Spinal Reflexes after Spinal Cord Injury

2011 ◽  
Vol 28 (2) ◽  
pp. 299-309 ◽  
Author(s):  
Marie-Pascale Côté ◽  
Gregory A. Azzam ◽  
Michel A. Lemay ◽  
Victoria Zhukareva ◽  
John D. Houlé
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neurotrophic Factors ◽  
Spinal Reflexes ◽  
Cord Injury ◽  
Activity Dependent

Responsiveness of the Neuromuscular Recovery Scale During Outpatient Activity-Dependent Rehabilitation for Spinal Cord Injury

2015 ◽  
Vol 30 (6) ◽  
pp. 528-538 ◽  
Author(s):  
Nicole J. Tester ◽  
Douglas J. Lorenz ◽  
Sarah P. Suter ◽  
Jeffrey J. Buehner ◽  
Daniel Falanga ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cord Injury ◽  
Activity Dependent

scholarly journals SPIKE-TRIGGERED INTRASPINAL MICROSTIMULATION IMPROVES MOTOR PERFORANCE IN AN AMBULATORY RAT MODEL OF SPINAL CORD INJURY

2021 ◽  
Author(s):  
Jordan A Borrell ◽  
Domenico Gattozzi ◽  
Dora Krizsan-Agbas ◽  
Randolph J. Nudo ◽  
SHAWN B FROST
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Cortex ◽  
Rat Model ◽  
Kinematic Analysis ◽  
Intraspinal Microstimulation ◽  
Custom Made ◽  
Cord Injury ◽  
And Control ◽  
Activity Dependent

The purpose of this study was to determine if spike-triggered intraspinal microstimulation (ISMS) results in improved motor performance in an ambulatory rat model of spinal cord injury (SCI). Experiments were carried out in adult male Sprague Dawley rats with 175 kdyn moderate T8 contusion injury. Rats were randomly assigned to one of two groups: Control or Activity Dependent Stimulation (ADS) therapy. Four weeks post-SCI, all rats were implanted with a recording electrode in the left hindlimb motor cortex and a fine-wire, custom-made stimulating electrode in the contralateral lumbar spinal cord. Intracortical and intraspinal microstimulation were used to find sites of similar hip representation areas, which were paired together for ADS therapy. In the ADS therapy group, spike-stimulus conditioning was administered for 4 hours/day, 4 days/week, for 4 weeks via a tethered cable in a testing chamber. During therapy sessions, single-unit spikes were discriminated in real time in the hindlimb motor cortex and used to trigger stimulation in the spinal cord ventral horn. The optimal stimulus intensity (50% ISMS movement threshold) and spike-stimulus delay (10ms) determined in preliminary anesthetized preparations were used during ADS. Control rats were similarly implanted with electrodes but did not receive stimulation therapy. Motor performances of each rat were evaluated before SCI contusion, once a week post-SCI for four weeks (prior to electrode implantation), and once a week post-conditioning for four weeks. Behavioral testing included BBB scoring, Ledged Beam walking, Horizontal Ladder walking, treadmill kinematics via the DigiGait and TreadScan system, and open field walking using OptiTrack kinematic analysis. BBB scores were significantly improved in ADS rats compared to Control rats after 1 week of therapy. In the ADS therapy rats, BBB scores were significantly improved after two weeks of ADS therapy when compared to pre-therapy. Foot fault scores on the Horizontal Ladder were significantly lower in ADS rats compared to pre-therapy ADS and Control rats after 1 week of therapy and returned to pre-injury measures after three weeks of ADS therapy. The Ledged Beam test and kinematic analysis using the DigiGait and TreadScan system showed deficits after SCI in both ADS and Control rats but there were no significant differences between groups after 4 weeks of ADS therapy. These results show that activity dependent stimulation after spinal cord injury using spike-triggered ISMS enhances behavioral recovery of locomotor function as measured by the BBB score and the Horizontal Ladder task.

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