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2. Intrinsic motoneuron properties in typical human development

Author

Mohammadalinejad, Ghazaleh, primary, Afsharipour, Babak, additional, Yacyshyn, Alex, additional, Duchcherer, Jennifer, additional, Bashuk, Jack, additional, Bennett, Erin, additional, Pearcey, Gregory E. P., additional, Negro, Francesco, additional, Quinlan, Katharina A., additional, Bennett, David J., additional, and Gorassini, Monica A., additional

Published
2024
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6. Post‐activation depression from primary afferent depolarization (PAD) produces extensor H‐reflex suppression following flexor afferent conditioning

Author

Metz, Krista, primary, Matos, Isabel Concha, additional, Hari, Krishnapriya, additional, Bseis, Omayma, additional, Afsharipour, Babak, additional, Lin, Shihao, additional, Singla, Rahul, additional, Fenrich, Keith K., additional, Li, Yaqing, additional, Bennett, David J, additional, and Gorassini, Monica A., additional

Published
2023
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8. Locomotor-related propriospinal V3 neurons produce primary afferent depolarization and modulate sensory transmission to motoneurons.

Author

Shihao Lin, Hari, Krishnapriya, Black, Sophie, Khatmi, Aysan, Fouad, Karim, Gorassini, Monica A., Yaqing Li, Lucas-Osma, Ana M., Fenrich, Keith K., and Bennett, David J.

Subjects
MOTOR neurons, GABAERGIC neurons, NEURONS, AFFERENT pathways, GLUTAMATE receptors, SPINAL cord, SENSORIMOTOR cortex
Abstract

When a muscle is stretched, sensory feedback not only causes reflexes but also leads to a depolarization of sensory afferents throughout the spinal cord (primary afferent depolarization, PAD), readying the whole limb for further disturbances. This sensoryevoked PAD is thought to be mediated by a trisynaptic circuit, where sensory input activates first-order excitatory neurons that activate GABAergic neurons that in turn activate GABAA receptors on afferents to cause PAD, though the identity of these firstorder neurons is unclear. Here, we show that these first-order neurons include propriospinal V3 neurons, as they receive extensive sensory input and in turn innervate GABAergic neurons that cause PAD, because optogenetic activation or inhibition of V3 neurons in mice mimics or inhibits sensory-evoked PAD, respectively. Furthermore, persistent inward sodium currents intrinsic to V3 neurons prolong their activity, explaining the prolonged duration of PAD. Also, local optogenetic activation of V3 neurons at one segment causes PAD in other segments, due to the long propriospinal tracts of these neurons, helping to explain the radiating nature of PAD. This in turn facilitates monosynaptic reflex transmission to motoneurons across the spinal cord. In addition, V3 neurons directly innervate proprioceptive afferents (including Ia), causing a glutamate receptor-mediated PAD (glutamate PAD). Finally, increasing the spinal cord excitability with either GABAA receptor blockers or chronic spinal cord injury causes an increase in the glutamate PAD. Overall, we show the V3 neuron has a prominent role in modulating sensory transmission, in addition to its previously described role in locomotion. NEW & NOTEWORTHY Locomotor-related propriospinal neurons depolarize sensory axons throughout the spinal cord by either direct glutamatergic axoaxonic contacts or indirect innervation of GABAergic neurons that themselves form axoaxonic contacts on sensory axons. This depolarization (PAD) increases sensory transmission to motoneurons throughout the spinal cord, readying the sensorimotor system for external disturbances. The glutamate-mediated PAD is particularly adaptable, increasing with either an acute block of GABA receptors or chronic spinal cord injury, suggesting a role in motor recovery. [ABSTRACT FROM AUTHOR]

Published
2023
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10. Early intensive leg training to enhance walking in children with perinatal stroke: Protocol for a randomized controlled trial

Author

Hurd, Caitlin, Livingstone, Donna, Brunton, Kelly, Teves, Michelle, Zewdie, Ephrem, Smith, Allison, Ciechanski, Patrick, Gorassini, Monica A., Kirton, Adam, Watt, Man-Joe, Andersen, John, Yager, Jerome, and Yang, jaynie F.

Subjects
Stroke (Disease) -- Prevention, Therapeutics, Physiological -- Usage -- Physiological aspects -- Methods, Physical therapy -- Usage -- Physiological aspects -- Methods, Children -- Physiological aspects -- Usage -- Methods, Physical therapy for children -- Usage -- Physiological aspects -- Methods, Walking -- Methods -- Physiological aspects -- Usage, Health
Abstract

Background. Development of motor pathways is modulated by activity in these pathways, when they are maturing (ie, critical period). Perinatal stroke injures motor pathways, including the corticospinal tracts, reducing their [...]

Published
2017
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14. Supplemental Material - Early, Intensive, Lower Extremity Rehabilitation Shows Preliminary Efficacy After Perinatal Stroke: Results of a Pilot Randomized Controlled Trial

Author

Hurd, Caitlin, Livingstone, Donna, Brunton, Kelly, Smith, Allison, Gorassini, Monica, Watt, Man-Joe, Andersen, John, Kirton, Adam, and Yang, Jaynie F.

Subjects
FOS: Clinical medicine, 110308 Geriatrics and Gerontology, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract

Supplemental Material for Early, Intensive, Lower Extremity Rehabilitation Shows Preliminary Efficacy After Perinatal Stroke: Results of a Pilot Randomized Controlled Trial by Caitlin Hurd, Donna Livingstone, Kelly Brunton, Allison Smith, Monica Gorassini, Man-Joe Watt, John Andersen, Adam Kirton, and Jaynie F. Yang in Neurorehabilitation and Neural Repair

Published
2022
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20. Recovery of motoneuron and locomotor function after spinal cord injury depends on constitutive activity in [5-HT.sub.2C] receptors

Author

Murray, Katherine C., Nakae, Aya, Stephens, Marilee J., Rank, Michelle, D'Amico, Jessica, Harvey, Philip J., Li, Xiaole, Harris, R. Luke W., Ballou, Edward W., Anelli, Roberta, Heckman, Charles J., Mashimo, Takashi, Vavrek, Romana, Sanelli, Leo, Gorassini, Monica A., Bennett, David J., and Fouad, Karim

Subjects
Neural transmission -- Health aspects -- Research -- Genetic aspects, Spinal cord injuries -- Complications and side effects -- Research -- Risk factors -- Genetic aspects -- Care and treatment
Abstract

Muscle paralysis after spinal cord injury is partly caused by a loss of brainstem-derived serotonin (5-HT), which normally maintains motoneuron excitability by regulating crucial persistent calcium currents. Here we examine how over time motoneurons compensate for lost 5-HT to regain excitability. We find that, months after a spinal transection in rats, changes in posttranscriptional editing of [5-HT.sub.2C] receptor mRNA lead to increased expression of [5- HT.sub.2C] receptor isoforms that are spontaneously active (constitutively active) without 5-HT. Such constitutive receptor activity restores large persistent calcium currents in motoneurons in the absence of 5-HT. We show that this helps motoneurons recover their ability to produce sustained muscle contractions and ultimately enables recovery of motor functions such as locomotion. However, without regulation from the brain, these sustained contractions can also cause debilitating muscle spasms. Accordingly, blocking constitutively active [5-HT.sub.2C] receptors with SB206553 or cyproheptadine, in both rats and humans, largely eliminates these calcium currents and muscle spasms, providing a new rationale for antispastic drug therapy., Severe spinal cord injury (SCI) causes an immediate paralysis of muscles innervated by motoneurons directly caudal to the injury site. This results not only from a loss of supraspinal tracts [...]

Published
2010
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22. GABA facilitates spike propagation through branch points of sensory axons in the spinal cord

Author

Hari, Krishnapriya, primary, Lucas-Osma, Ana M., additional, Metz, Krista, additional, Lin, Shihao, additional, Pardell, Noah, additional, Roszko, David A., additional, Black, Sophie, additional, Minarik, Anna, additional, Singla, Rahul, additional, Stephens, Marilee J., additional, Pearce, Robert A., additional, Fouad, Karim, additional, Jones, Kelvin E., additional, Gorassini, Monica A., additional, Fenrich, Keith K., additional, Li, Yaqing, additional, and Bennett, David J., additional

Published
2021
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24. Delta F Supplemental tables March 31

Author

Afsharipour, Babak, Manzur, Nagib, Duchcherer, Jennifer, Fenrich, Keith, Negro, Francesco, Quinlan, Kathy A., Bennett, David Jonathan, and Gorassini, Monica A.

Subjects
Quantitative Biology::Neurons and Cognition
Abstract

Estimation of self-sustained activity from persistent inward currents using firing rate profiles of multiple motor units in humans

Published
2020
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25. Spinal and brain control of human walking: implications for retraining of walking

Author

Yang, Jaynie F. and Gorassini, Monica

Subjects
Brain research -- Research, Spinal cord injuries -- Research, Walking -- Research, Psychology and mental health, Research
Abstract

In this update, the authors will discuss evidence for both spinal and brain regulation of walking in humans. They will consider the sensory control of walking in young babies and [...]

Published
2006

29. Volitional muscle strength in the legs predicts changes in walking speed following locomotor training in people with chronic spinal cord injury

Author

Yang, Jaynie F., Norton, Jonathan, Nevett-Duchcherer, Jennifer, Roy, Francois D., Gross, Douglas P., and Gorassini, Monica A.

Subjects
Muscle strength -- Physiological aspects -- Research, Extremities, Lower -- Physiological aspects -- Research, Spinal cord injuries -- Care and treatment -- Research, Leg -- Physiological aspects -- Research, Walking -- Physiological aspects -- Research, Health
Abstract

Background. It is unclear which individuals with incomplete spinal cord injury best respond to body-weight-supported treadmill training. Objective. The purpose of this study was to determine the factors that predict whether a person with motor incomplete spinal cord injury will respond to bodyweight-supported treadmill training. Design. This was a prognostic study with a one-group pretest-posttest design. Methods. Demographic, clinical, and electrophysiological measurements taken prior to training were examined to determine which measures best predicted improvements in walking speed in 19 individuals with chronic (>7 months postinjury), motor-incomplete spinal cord injuries (ASIA Impairment Scale categories C and D, levels C1-L1). Results. Two initial measures correlated significantly with improvements in walking speed: (1) the ability to volitionally contract a muscle, as measured by the lower-extremity manual muscle test (LE MMT) (r=.72), and (2) the peak locomotor electromyographic (EMG) amplitude in the legs (r=.56). None of the demographics (time since injury, age, body mass index) were significantly related to improvements in walking speed, nor was the clinical measure of balance (Berg Balance Scale). Further analysis of LE MMT scores showed 4 key muscle groups were significantly related to improvements in walking speed: knee extensors, knee flexors, ankle plantar flexors, and hip abductors (r=.82). Prediction using the summed MMT scores from those muscles and peak EMG amplitude in a multivariable regression indicated that peak locomotor EMG amplitude did not add significantly to the prediction provided by the LE MMT alone. Change in total LE MMT scores from the beginning to the end of training was not correlated with a change in walking speed over the same period. Limitations. The sample size was limited, so the results should be considered exploratory. Conclusions. The results suggest that preserved muscle strength in the legs after incomplete spinal cord injury, as measured by MMT, allows for improvements in walking speed induced by locomotor training., Intensive, body-weight-supported treadmill training (BWSTT) is an effective way to improve overground walking in individuals with spinal cord injury (SCI). (1,2) Individuals in ASIA Impairment Scale (AIS) categories C and [...]

Published
2011
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32. List of Contributors

Author

Ashizawa, Tetsuo, primary, Baier, P.C., additional, Becker, Lore, additional, Bennett, David J., additional, Berke, Brett, additional, Betarbet, Ranjita, additional, Bhatia, Kailash P., additional, Bibbiani, Francesco, additional, Blake, David T., additional, Borchelt, David R., additional, Bose, Prodip, additional, Bragg, D. Cristopher, additional, Brashear, Allison, additional, Breakefield, Xandra O., additional, Bressman, Susan, additional, Burke, Kathleen, additional, Byl, Nancy N., additional, Caldwell, Guy A., additional, Caldwell, Kim A., additional, Cao, Songsong, additional, Cenci, M. Angela, additional, Chesselet, Marie-Françoise, additional, Colosimo, Carlo, additional, Dang, Mai, additional, Dennis, Julie A., additional, Devys, Didier, additional, Dietrich, Paula, additional, Dragatsis, Ioannis, additional, D'Souza, Ian, additional, Elble, Rodger J., additional, Evinger, Craig, additional, Fernagut, Pierre-Olivier, additional, Fernandez, Hubert H., additional, Fink, John K., additional, Fleming, Sheila M., additional, Fletcher, Colin F., additional, Fox, Lyle, additional, Fowler, Stephen C., additional, Friedman, Joseph H., additional, Geser, Felix, additional, Ghorayeb, Imad, additional, Gorassini, Monica, additional, Greenamyre, J. Timothy, additional, Harvey, Philip J., additional, Heales, Simon J.R., additional, Healy, Peter J., additional, Helmlinger, Dominique, additional, Hess, Ellen J., additional, Hillman, Ralph, additional, Homanics, Gregg E., additional, Hyland, Keith, additional, Izevbaye, Iyare, additional, Jackson-Lewis, Vernice, additional, Jinnah, H.A., additional, Jurkowski, Anita J., additional, Kassem, Iris S., additional, Kaytor, Michael D., additional, Kralic, Jason E., additional, LeDoux, Mark, additional, Lewis, Jada, additional, Li, Yuqing, additional, Lieberman, David, additional, Linn, Gary S., additional, Litvan, Irene, additional, Lombroso, Paul J., additional, Louis, Elan D., additional, Lundblad, Martin, additional, Marsh, J. Lawrence, additional, McGowan, Eileen, additional, McKerchar, T.L., additional, Merzenich, Michael, additional, Morrow, A. Leslie, additional, Naquet, Robert, additional, Nass, Richard, additional, Navas, Parvoneh Poorkaj, additional, O'Buckley, Todd K., additional, Oh, Justin D., additional, Ohye, Chihiro, additional, Orr, Harry T., additional, Osterman, Jessica L., additional, Pallanck, Leo J., additional, Pandolfo, Massimo, additional, Pendleton, Robert G., additional, Peng, Haixiang, additional, Peng, I-Feng, additional, Perez, Dianne M., additional, Perlman, Susan L., additional, Perlmutter, Joel S., additional, Petravicz, Jeremy, additional, Pfeiffer, Ronald F., additional, Phillips, James O., additional, Pranzatelli, Michael R., additional, Pulst, Stefan-M., additional, Rainier, Shirley, additional, Rao, Jayaraman, additional, Richter, Angelika, additional, Robinson, Farrel R., additional, Ross, Christopher A., additional, Sachdev, Perminder S., additional, Saunders-Pullman, Rachel, additional, Schellenberg, Gerard D., additional, Schilling, Gabriele, additional, Schofield, Peter R., additional, Sharma, Nutan, additional, Sherer, Todd B., additional, Silva-Barrat, Carmen, additional, Singer, Harvey S., additional, Smeyne, Richard Jay, additional, Smith-Hicks, Constance, additional, Stacy, Mark, additional, Stafanova, Nadia, additional, Standaert, David G., additional, Subramony, S.H., additional, Tabbal, Samer D., additional, Tai, Kwok-Keung, additional, Thompson, Floyd J., additional, Thompson, Leslie M., additional, Tison, François, additional, Trenkwalder, Claudia, additional, Truong, Daniel D., additional, Ueda, Atsushi, additional, Vartiainen, Suvi, additional, Weiher, Hans, additional, Weiss, Avery H., additional, Wenning, Gregor Karl, additional, Whitworth, Alexander J., additional, Windsor, Peter A., additional, Wong, Garry, additional, Wu, Chun-Fang, additional, and Zarcone, T.J., additional

Published
2005
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36. Additional file 1: of Retraining walking over ground in a powered exoskeleton after spinal cord injury: a prospective cohort study to examine functional gains and neuroplasticity

Author

Khan, Atif, Livingstone, Donna, Hurd, Caitlin, Duchcherer, Jennifer, Misiaszek, John, Gorassini, Monica, Manns, Patricia, and Jaynie Yang

Abstract

Contains results from sensory testing, transcranial magnetic stimulation, changes in walking skill and distance after long breaks in training. (PDF 202 kb)

Published
2019
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39. Supplemental_Materials – Supplemental material for Full Activation Profiles and Integrity of Corticospinal Pathways in Adults With Bilateral Spastic Cerebral Palsy

Author

Condliffe, Elizabeth G., Jeffery, Dean T., Emery, Derek J., Treit, Sarah, Beaulieu, Christian, and Gorassini, Monica A.

Subjects
FOS: Clinical medicine, 110308 Geriatrics and Gerontology, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract

Supplemental material, Supplemental_Materials for Full Activation Profiles and Integrity of Corticospinal Pathways in Adults With Bilateral Spastic Cerebral Palsy by Elizabeth G. Condliffe, Dean T. Jeffery, Derek J. Emery, Sarah Treit, Christian Beaulieu and Monica A. Gorassini in Neurorehabilitation and Neural Repair

Published
2018
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44. Peripheral sensory activation of cortical circuits in the leg motor cortex of man

Author

Roy, François D and Gorassini, Monica A

Subjects
Adult, Male, Leg, Electromyography, Motor Cortex, Middle Aged, Evoked Potentials, Motor, Electric Stimulation, Time, Physical Stimulation, Humans, Female, Neurons, Afferent, Muscle, Skeletal, Neuroscience
Abstract

Peripheral sensory afferents in the hand activate both excitatory and inhibitory intracortical circuits to potentially facilitate and prune descending motor commands. In this study, we characterized how afferent inputs modulate the excitability of cortical circuits in the leg area of the primary motor cortex by examining how stimulation of the tibial nerve (TN) at the ankle alters motor evoked potentials (MEPs) activated by transcranial magnetic stimulation (TMS). Resting MEPs in the tibialis anterior (TA) muscle were facilitated in response to heteronymous activation of the TN 45-50 ms earlier, whereas MEPs were inhibited at interstimulus intervals of 32.5-37.5 ms. Similar time-dependent modulation occurred in the soleus (SOL) muscle with stimulation of the homonymous posterior tibial nerve (PTN) at the knee. To determine the site of this afferent-evoked facilitation and inhibition (spinal or cortical), we compared the effects of afferent stimulation to responses evoked at subcortical sites. At interstimulus intervals where MEP facilitation was observed (near 50 ms), spinal H-reflexes and responses evoked from corticospinal tract stimulation at the brainstem were predominantly depressed by the sensory stimulus suggesting that the observed MEP facilitation was cortical in origin. At interstimulus intervals where MEP depression was observed (near 35 ms), brainstem evoked responses were depressed to a similar degree and, in contrast to the hand, this suggests that spinal rather than cortical circuits mediate short-latency afferent inhibition (SAI) of leg MEPs. When the MEP was facilitated by afferent inputs, short-interval intracortical inhibition (SICI) was reduced and intracortical facilitation (ICF) was increased, but long-interval intracortical inhibition (LICI) at a 100 ms interval was unchanged. In addition, sensory excitation increased the recruitment of early, middle and late descending corticospinal volleys as evidenced from increases in MEP facilitation at the corresponding I-wave periodicity. We propose that sensory activation from the leg has a diffuse and predominantly facilitatory effect on the leg primary motor cortex.

Published
2008

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