scholarly journals Spinal Cord Injury Significantly Alters the Properties of Reticulospinal Neurons: I. Biophysical Properties, Firing Patterns, Excitability, and Synaptic Inputs

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1921
Author(s):  
Ryan A. Hough ◽  
Timothee Pale ◽  
Jessica A. Benes ◽  
Andrew D. McClellan

Following spinal cord injury (SCI) for larval lampreys, descending axons of reticulospinal (RS) neurons regenerate, and locomotor function gradually recovers. In the present study, the electrophysiological properties of uninjured (left)-injured (right) pairs of large, identified RS neurons were compared following rostral, right spinal cord hemi-transections (HTs). First, changes in firing patterns of injured RS neurons began in as little as 2–3 days following injury, these changes were maximal at ~2–3 weeks (wks), and by 12–16 wks normal firing patterns were restored for the majority of neurons. Second, at ~2–3 wks following spinal cord HTs, injured RS neurons displayed several significant changes in properties compared to uninjured neurons: (a) more hyperpolarized VREST; (b) longer membrane time constant and larger membrane capacitance; (c) increased voltage and current thresholds for action potentials (APs); (d) larger amplitudes and durations for APs; (e) higher slope for the repolarizing phase of APs; (f) virtual absence of some afterpotential components, including the slow afterhyperpolarization (sAHP); (g) altered, injury-type firing patterns; and (h) reduced average and peak firing (spiking) frequencies during applied depolarizing currents. These altered properties, referred to as the “injury phenotype”, reduced excitability and spiking frequencies of injured RS neurons compared to uninjured neurons. Third, artificially injecting a current to add a sAHP waveform following APs for injured neurons or removing the sAHP following APs for uninjured neurons did not convert these neurons to normal firing patterns or injury-type firing patterns, respectively. Fourth, trigeminal sensory-evoked synaptic responses recorded from uninjured and injured pairs of RS neurons were not significantly different. Following SCI, injured lamprey RS neurons displayed several dramatic changes in their biophysical properties that are expected to reduce calcium influx and provide supportive intracellular conditions for axonal regeneration.

Brain ◽  
2008 ◽  
Vol 131 (6) ◽  
pp. 1478-1491 ◽  
Author(s):  
J. A. Norton ◽  
D. J. Bennett ◽  
M. E. Knash ◽  
K. C. Murray ◽  
M. A. Gorassini

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Haddy Alas ◽  
Avery Brown ◽  
Katherine Pierce ◽  
Cole Bortz ◽  
Michael Moses ◽  
...  

Abstract INTRODUCTION As youth athletic sports continue to be played at a highly competitive level, more attention is called to potentially fatal cervical spine injuries. METHODS KID was queried for patients with E-Codes (ICD-9-CM codes) pertaining to external causes of injury secondary to sports-related activities from 2003 to 2012. Patients were further grouped by cervical spine injury type [C 1-4 and C 5-7 fracture with and without spinal cord injury (SCI), dislocation, and SCI without radiographic abnormality (SCIWORA). Patients were grouped by age into children (4-9), preadolescents (pre,10-13), and adolescents (14-17). Sports included by E-Code: American football, other team sports, individual, winter, water, and martial arts. Kruskall–Wallis tests with posthocs identified differences in cervical injury type across age groups and sports. Logistic regression assessed predictors of traumatic brain injury (TBI) and cervical injury type. RESULTS A total of 38 539 pts with sports injuries were identified (12.76 yr, 24.5% F). Adolescents had the highest rate of sports injuries per year, but rates decreased in pre and adolescents and increased in children. Adolescents had the highest rate of any type of cervical spine injury and TBI. Adolescence increased odds for C 1-4 fx with and without SCI, C 5-7 fx with and without SCI, cervical dislocation, and cervical SCIWORA (all P < .05). Cervical fx of any type tended to occur in disproportionately higher rates via team, winter, or water sports (P < .001). Martial arts had significantly higher rates of cervical dislocations compared to other sports (P = .039). Football injuries rose from 5.83% to 9.14% (2009-2012) (P < .001) and had significantly more SCIWORA than non-football sports (1.6 vs 1.0%, P = .012). Football increased odds of SCI by 1.56x compared to any other sport (OR: 1.56 [1.11-2.20], P = .011). SCIWORA was a significant predictor for concurrent TBI across all sports (OR: 2.35[1.77-3.11], P < .001). CONCLUSION Adolescent athletes had the highest rates of upper/lower cervical fracture, dislocation, and SCIWORA. Adolescence and SCIWORA were significant predictors of concurrent TBI across sports.


2019 ◽  
Vol 121 (4) ◽  
pp. 1352-1367 ◽  
Author(s):  
Shihao Lin ◽  
Yaqing Li ◽  
Ana M. Lucas-Osma ◽  
Krishnapriya Hari ◽  
Marilee J. Stephens ◽  
...  

Spinal cord injury leads to a devastating loss of motor function and yet is accompanied by a paradoxical emergence of muscle spasms, which often involve complex muscle activation patterns across multiple joints, reciprocal muscle timing, and rhythmic clonus. We investigated the hypothesis that spasms are a manifestation of partially recovered function in spinal central pattern-generating (CPG) circuits that normally coordinate complex postural and locomotor functions. We focused on the commissural propriospinal V3 neurons that coordinate interlimb movements during locomotion and examined mice with a chronic spinal transection. When the V3 neurons were optogenetically activated with a light pulse, a complex coordinated pattern of motoneuron activity was evoked with reciprocal, crossed, and intersegmental activity. In these same mice, brief sensory stimulation evoked spasms with a complex pattern of activity very similar to that evoked by light, and the timing of these spasms was readily reset by activation of V3 neurons. Given that V3 neurons receive abundant sensory input, these results suggest that sensory activation of V3 neurons is alone sufficient to generate spasms. Indeed, when we silenced V3 neurons optogenetically, sensory evoked spasms were inhibited. Also, inhibiting general CPG activity by blocking N-methyl-d-aspartate (NMDA) receptors inhibited V3 evoked activity and associated spasms, whereas NMDA application did the opposite. Furthermore, overwhelming the V3 neurons with repeated optogenetic stimulation inhibited subsequent sensory evoked spasms, both in vivo and in vitro. Taken together, these results demonstrate that spasms are generated in part by sensory activation of V3 neurons and associated CPG circuits. NEW & NOTEWORTHY We investigated whether locomotor-related excitatory interneurons (V3) play a role in coordinating muscle spasm activity after spinal cord injury (SCI). Unexpectedly, we found that these neurons not only coordinate reciprocal motor activity but are critical for initiating spasms, as well. More generally, these results suggest that V3 neurons are important in initiating and coordinating motor output after SCI and thus provide a promising target for restoring residual motor function.


2017 ◽  
Author(s):  
◽  
Ryan Anthony Hough

Following a severe spinal cord injury (SCI), the descending axons of reticulospinal (RS) neurons are damaged, resulting in paralysis below the site of the injury. For higher vertebrates, including humans, RS neurons are unable to regenerate their axons through the spinal lesion, resulting in permanent loss of voluntary motor control below the site of the injury. Conversely, some lower vertebrates, such as the lamprey, posses the remarkable ability to restore locomotor behavior below the site of the injury within weeks. This is possible because the central nervous system of the lamprey is a permissive environment for regeneration, and the injured RS neurons undergodramatic changes that are collectively referred to as the "injury phenotype" The present study investigated several mechanisms that might contribute to the injury phenotype. First, for injured lamprey RS neurons, a delayed membrane repolarization was activated at depolarizing potentials just below as well as above threshold, while for uninjured RS neurons the repolarization was mostly absent below threshold. Current and voltage clamp experiments were preformed to characterize the current mediating the delayed repolarization, as well as to estimate the effective activation voltage of these channels for injured and uninjured RS neurons. Additionally, pharmacology experiments indicated that the delayed membrane repolarization was significantly reduced in the presence of voltage-gated potassium channel blockers, and thus following SCI, there might be an up-regulation of outward rectifying potassium channels for injured lamprey RS neurons to reduce excitability. Second, for injured RS neurons, it appears that voltage-gated sodium channels are also up-regulated, but to a lesser degree than the voltage-gated potassium channels. This was tested by applying low doses of TTX to uninjured RS neurons to partially block voltage-gated sodium channels to experimentally simulate a differential increase in conductance for voltage-gated potassium channels. Applying low doses of TTX converted uninjured RS neurons from displaying normal biophysical properties, to displaying aspects of the "injury phenotype" such as altered firing properties and membrane resonance. Together, these possible neuronal changes account for many components of the "injury phenotype" seen in individual action potentials, as well as in repetitive firing. Understanding the neuronal changes that mediate the injury phenotype is critical, because these changes presumably create a cellular environment supportive for robust axonal regeneration. This and other knowledge will be critical for developing therapies to promote axonal regeneration and treat SCI in higher vertebrates, including hopefully one day, humans.


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