Stimulation of the spinal cord of decerebrated rat with double pulses

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

Analysis of responses on electrical stimulation is one of the experimental paradigms to study the excitability of the nervous system. In particular, the technique of recording muscle responses evoked by electrical epidural stimulation (ES) of the spinal cord (SC) in humans and animals is widely used. In rats decerebrated at the precollicular level, responses of mm. tibialis anterior (TA) and gastrocnemius medialis (GM) on ES of the L2, L4, L6 spinal segments and transvertebral stimulation (TS) of the VL2, VL4, VL6 vertebrae with single and double pulses were analyzed. The currents at which the amplitude of the sensory component of the response for a single pulse and one of the pulses of the pair was maximum were determined. At the minimum of these currents, the ratio of the amplitudes of the sensory component of the response to the first and second pulses to the amplitude of the sensory component of the response to a single pulse was analyzed. For both muscles, a weakening of the response to both pulses of the pair was obtained with TS VL2 and VL4, while when stimulating VL2, the TA response to the second pulse was lower than to the first. On the contrary, with ES of all segments of interest, a facilitation of the response to the second pulse was obtained for both muscles. A similar facilitation was qualitatively observed for two other muscles, mm. iliacus and vastus lateralis. Thus, the use of double pulses during stimulation made it possible to identify the dependence of the response of SC neural networks on the method of their activation (TS or ES). The facilitation of the response to the second pulse during ES is presumably explained by a decrease in presynaptic inhibition due to decerebration.

Full Text

Restricted Access

About the authors

V. A. Lyakhovetskii

Pavlov Institute of Physiology of the Russian Academy of Sciences

Email: mer-natalia@yandex.ru
Russian Federation, St. Petersburg

P. Yu. Shkorbatova

Pavlov Institute of Physiology of the Russian Academy of Sciences

Email: mer-natalia@yandex.ru
Russian Federation, St. Petersburg

O. V. Gorsky

Pavlov Institute of Physiology of the Russian Academy of Sciences; Saint-Petersburg State University

Email: mer-natalia@yandex.ru
Russian Federation, St. Petersburg; St. Petersburg

N. V. Pavlova

Pavlov Institute of Physiology of the Russian Academy of Sciences

Email: mer-natalia@yandex.ru
Russian Federation, St. Petersburg

E. Yu. Bazhenova

Pavlov Institute of Physiology of the Russian Academy of Sciences

Email: mer-natalia@yandex.ru
Russian Federation, St. Petersburg

P. E. Musienko

Pavlov Institute of Physiology of the Russian Academy of Sciences; Saint-Petersburg State University

Author for correspondence.
Email: mer-natalia@yandex.ru
Russian Federation, St. Petersburg; St. Petersburg

N. S. Merkulyeva

Pavlov Institute of Physiology of the Russian Academy of Sciences

Email: pol-spb@mail.ru
Russian Federation, St. Petersburg

References

  1. McLeod JG, Van der Meulen JP (1967) Effect of cerebellar ablation on the H reflex in the cat. Arch Neurol 16: 421–432. https://doi.org/10.1001/archneur.1967.00470220085010
  2. Lavrov I, Gerasimenko YP, Ichiyama RM, Courtine G, Zhong H, Roy RR, Edgerton VR (2006) Plasticity of spinal cord reflexes after a complete transection in adult rats: relationship to stepping ability. J Neurophysiol 96: 1699–1710. https://doi.org/10.1152/jn.00325.2006
  3. Hofstoetter US, Freundl B, Binder H, Minassian K (2019) Recovery cycles of posterior root-muscle reflexes evoked by transcutaneous spinal cord stimulation and of the H reflex in individuals with intact and injured spinal cord. PLoS One 14: e0227057. https://doi.org/10.1371/journal.pone.0227057
  4. Sharma P, Shah PK (2021) In vivo electrophysiological mechanisms underlying cervical epidural stimulation in adult rats. J Physiol 599: 3121–3150. https://doi.org/10.1113/JP281146
  5. Gerasimenko YP, Lavrov IA, Courtine G, Ichiyama RM, Dy CJ, Zhong H, Roy RR, Edgerton VR (2006) Spinal cord reflexes induced by epidural spinal cord stimulation in normal awake rats. J Neurosci Methods 157: 253–263. https://doi.org/10.1016/j.jneumeth.2006.05.004
  6. Courtine G, Harkema SJ, Dy CJ, Gerasimenko YP, Dyhre-Poulsen P (2007) Modulation of multisegmental monosynaptic responses in a variety of leg muscles during walking and running in humans. J Physiol 582(Pt 3): 1125–1139. https://doi.org/10.1113/jphysiol.2007.128447
  7. Roy FD, Gibson G, Stein RB (2012) Effect of percutaneous stimulation at different spinal levels on the activation of sensory and motor roots. Exp Brain Res 223: 281–289. https://doi.org/10.1007/s00221-012-3258-6
  8. Verma R, Virdi JK, Singh N, Jaggi AS (2019) Animals models of spinal cord contusion injury. Korean J Pain 32: 12–21. https://doi.org/10.3344/kjp.2019.32.1.12
  9. Павлова НВ, Богачева ИН, Баженова ЕЮ, Горский ОВ, Мошонкина ТР, Герасименко ЮП (2019) Восстановление двигательных функций у спинализированных крыс при электрической стимуляции спинного мозга и локомоторной тренировкe. Росс физиол журн им ИМ Сеченова 105: 565–577. [Pavlova NV, Bogacheva IN, Bazhenova EJu, Gorskiy OV, Moshonkina TR, Gerasimenko YuP (2019) Restoration of motor functions in spinal rats by electrical stimulation of the spinal cord and locomotor training. Ross Fiziol Zh Im I M Sechenova 105: 565–577. (In Russ)]. https://doi.org/10.1134/S086981391905008X
  10. Malloy DC, Knikou M, Côté M-P (2022) Adapting human-based transcutaneous spinal cord stimulation to develop a clinically relevant animal model. J Clinical Medicine 11: 2023. https://doi.org/10.3390/jcm11072023
  11. Shkorbatova P, Lyakhovetskii V, Pavlova N, Popov A, Bazhenova E, Kalinina D, Gorskii O, Musienko P (2020) Mapping of the spinal sensorimotor network by transvertebral and transcutaneous spinal cord stimulation. Frontiers in systems neuroscience 14: 555593. https://doi.org/10.3389/fnsys.2020.555593
  12. Nicolopoulos-Stournaras S, Iles JF (1984) Hindlimb muscle activity during locomotion in the rat (Rattus norvegicus) (Rodentia: Muridae). J Zool Lond 203: 427–440. https://doi.org/10.1111/j.1469-7998.1984.tb02342.x
  13. Nakanishi ST, Whelan PJ (2012) A decerebrate adult mouse model for examining the sensorimotor control of locomotion. J Neurophysiol 107: 500–515. https://doi.org/10.1152/jn.00699.2011
  14. Skinner RD, Garcia-Rill E (1984) The mesencephalic locomotor region (MLR) in the rat. Brain Res 323: 385–389. https://doi.org/10.1016/0006-8993(84)90319-6
  15. Шкорбатова ПЮ, Ляховецкий ВА, Горский ОВ, Павлова НВ, Баженова ЕЮ, Калинина ДС, Мусиенко ПЕ, Меркульева НС (2023) Электрическая эпидуральная стимуляция спинного мозга децеребрированной крысы. Росс физиол журн им ИМ Сеченова 109: 798–816. [Shkorbatova PYu, Lyakhovetskii VA, Gorskiy OV, Pavlova NV, Bazhenova EJu, Kalinina DS, Musienko PE, Merkulyeva NS (2023) Electric epidural stimulation of the spinal cord of the decerebrated rat. Ross Fiziol Zh Im I M Sechenova 109: 798–816. (In Russ)]. https://doi.org/10.31857/S0869813923060092
  16. Capogrosso M, Wenger N, Raspopovic S, Musienko P, Beauparlant J, Bassi Luciani L, Courtine G, Micera S (2013) A computational model for epidural electrical stimulation of spinal sensorimotor circuits. J Neurosci 33: 19326–19340. https://doi.org/10.1523/JNEUROSCI.1688-13.2013
  17. Ghali GZ, Ghali MGZ (2020) Microneurosurgical techniques and perioperative strategies utilized to optimize experimental supracollicular decerebration in rats. J integrative neurosci 19: 137–177. https://doi.org/10.31083/j.jin.2020.01.1153
  18. Gilerovich EG, Moshonkina TR, Fedorova EA, Shishko TT, Pavlova NV, Gerasimenko YP, Otellin VA (2008) Morphofunctional characteristics of the lumbar enlargement of the spinal cord in rats. Neurosci Behav Physiol 38: 855–860. https://doi.org/10.1007/s11055-008-9056-8
  19. Wenger N, Moraud EM, Gandar J, Musienko P, Capogrosso M, Baud L, Le Goff CG, Barraud Q, Pavlova N, Dominici N, Minev IR, Asboth L, Hirsch A, Duis S, Kreider J, Mortera A, Haverbeck O, Kraus S, Schmitz F, DiGiovanna J, van den Brand R, Bloch J, Detemple P, Lacour SP, Bézard E, Micera S, Courtine G. (2016) Spatiotemporal neuromodulation therapies engaging muscle synergies improve motor control after spinal cord injury. Nat Med 22: 138–145. https://doi.org/10.1038/nm.4025
  20. Curtis DR, Eccles JC (1960) Synaptic action during and after repetitive stimulation. J Physiol 150: 374–398. https://doi.org/10.1113/jphysiol.1960.sp006393
  21. Granit R (1950) Reflex self-regulation of muscle contraction and autogenetic inhibition. J Neurophysiol 13: 351–372. https://doi.org/10.1152/jn.1950.13.5.351
  22. Lloyd DP, Wilson VJ (1957) Reflex depression in rhythmically active monosynaptic reflex pathways. J Gen Physiol 40: 409–426. https://doi.org/10.1085/jgp.40.3.409
  23. Minassian K, Jilge B, Rattay F, Pinter MM, Binder H, Gerstenbrand F, Dimitrijevic MR (2004) Stepping-like movements in humans with complete spinal cord injury induced by epidural stimulation of the lumbar cord: electromyographic study of compound muscle action potentials. Spinal Cord 42:401–416. https://doi.org/10.1038/sj.sc.3101615
  24. Dideriksen JL, Muceli S, Dosen S, Laine CM, Farina D (2015) Physiological recruitment of motor units by high-frequency electrical stimulation of afferent pathways. J Appl Physiol (1985). 118: 365–376. https://doi.org/10.1152/japplphysiol.00327.2014
  25. Jaumard NV, Leung J, Gokhale AJ, Guarino BB, Welch WC, Winkelstein BA (2015) Relevant anatomic and morphological measurements of the rat spine. Spine 40: E1084–E1092. https://doi.org/10.1097/BRS.0000000000001021
  26. Mohan R, Tosolini AP, Morris R (2015) Segmental distribution of the motor neuron columns that supply the rat hindlimb: A muscle/motor neuron tract-tracing analysis targeting the motor end plates. Neuroscience 307: 98–108. https://doi.org/10.1016/j.neuroscience.2015.08.030
  27. Wilson VJ, Talbot WH, Diecke FP (1960) Distribution of recurrent facilitation and inhibition in cat spinal cord. J Neurophysiol 23: 144–153.
  28. Tanabe M, Kaneko T (1996) Paired pulse facilitation of GABAergic IPSCs in ventral horn neurons in neonatal rat spinal cord. Brain Res 716:101–106. https://doi.org/10.1016/0006-8993(96)00051-0
  29. Meinck HM (1976). Occurrence of the H reflex and the F wave in the rat. Electroencephalogr Clin Neurophysiol 41: 530–533. https://doi.org/10.1016/0013-4694(76)90064-x
  30. Calancie B, Broton JG, Klose KJ, Traad M, Difini J, Ayyar DR (1993) Evidence that alterations in presynaptic inhibition contribute to segmental hypo- and hyperexcitability after spinal cord injury in man. Electroencephalogr Clin Neurophysiol 89: 177–186. https://doi.org/10.1016/0168-5597(93)90131-8
  31. Andrews JC, Roy FD, Ba F, Sankar T (2020). Intraoperative changes in the H-reflex pathway during deep brain stimulation surgery for Parkinson’s disease: A potential biomarker for optimal electrode placement. Brain Stimul 13: 1765–1773. https://doi.org/10.1016/j.brs.2020.09.024
  32. Ho SM, Waite PM (2002) Effects of different anesthetics on the paired-pulse depression of the h reflex in adult rat. Exp Neurol 177: 494–502. https://doi.org/10.1006/exnr.2002.8013
  33. Guiho T, Baker SN, Jackson A (2021) Epidural and transcutaneous spinal cord stimulation facilitates descending inputs to upper-limb motoneurons in monkeys. J Neural Eng 18: 046011. https://doi.org/10.1088/1741-2552/abe358
  34. Taylor BA, Fennelly ME, Taylor A, Farrell J (1993) Temporal summation – the key to motor evoked potential spinal cord monitoring in humans. J Neurol Neurosurg Psychiatry 56: 104–106.
  35. Zhang W, Schneider SP (2011). Short-term modulation at synapses between neurons in laminae II–V of the rodent spinal dorsal horn. J Neurophysiol 105:2920–2930. https://doi.org/10.1152/jn.00684.2010
  36. Floeter MK, Lev-Tov A (1993) Excitation of lumbar motoneurons by the medial longitudinal fasciculus in the in vitro brain stem spinal cord preparation of the neonatal rat. J Neurophysiol 70: 2241–2250. https://doi.org/10.1152/jn.1993.70.6.2241
  37. Lyakhovetskii V, Shkorbatova P, Gorskii O, Musienko P. (2022) Forward stepping evoked by transvertebral stimulation in the decerebrate cat. Neuromodulation S1094–7159(22)01373–3.

Supplementary files

Supplementary Files
Action
1. JATS XML
2. Fig. 1. Schematic diagram of the experiment on transvertebral and epidural stimulation of the rat spinal cord. (a) – schematic diagram of the experimental setup. Decerebration – decerebration zone, stimulation – fixation zone of the stimulating electrode, TA – m. tibialis anterior, GM – m. gastrocnemius medialis; (b) – position of the vertebral and epidural stimulating electrodes relative to the vertebra and spinal cord, dorsal roots – dorsal roots of the spinal cord, ventral roots – ventral roots of the spinal cord, DRG – dorsal root ganglion; (c) Determination of the amplitudes of the sensory component of a single (H) pulse and the first (H1) and second (H2) pulses during paired stimulation. Using the example of the average evoked response of the right GM during transvertebral stimulation of VL2 of rat #9 at a current of 900 μA.

Download (157KB)
3. Fig. 2. Dependence of evoked potentials on stimulation current: (a) – change in evoked muscle responses to double pulses as current increases during transvertebral (TS) and epidural stimulation (ES). Five individual muscle responses are shown for each current. Using the example of the right m. gastrocnemius medialis (GM) and m. tibialis anterior (TA) during TS VL2 and ES L2 of rat #9. Stim – stimulation channel. ER – early, motor components of the muscle response, MR – middle, sensory monosynaptic components of the muscle response; (b) – recruitment curves during TS (left) and ES (right). H, H1, H2 – amplitudes of the sensory component of the response to a single pulse and to the first and second pulses of a pair, respectively. The dotted rectangle highlights the values ​​used in further analysis. Using the example of GM in TS VL2 and ES L2 of rat #9.

Download (526KB)
4. Fig. 3. Characteristics of the sensory component of the response of m. tibialis anterior (TA) and m. gastrocnemius medialis (GM) during transvertebral stimulation with an interstimulus interval of 20 ms: (a) — currents at which the maximum sensory response to a single (H) and the first of a pair (H1) impulse was recorded during stimulation of the vertebrae VL2, VL4, VL6. *, ** — p < 0.05, p < 0.01 differences between stimulation currents; (b) Ratios of the amplitudes of the sensory components of the response to the first and second impulses of a pair to the response to a single impulse (H1/H and H2/H, respectively). #, ##, ### – p < 0.05, p < 0.01, p < 0.001 differences from the response to a single impulse, *, ** – p < 0.05, p < 0.01 differences between the responses to the first and second impulses of the pair.

Download (225KB)
5. Fig. 4. Characteristics of the sensory component of the response of m. tibialis anterior (TA) and m. gastrocnemius medialis (GM) during epidural stimulation with an interstimulus interval of 20 ms: (a) Currents at which the maximum sensory response to a single (H) and the second of a pair (H2) impulse was recorded during stimulation of segments (Segment) L2, L4, L6. * – p < 0.05 difference between stimulation currents; (b) Ratios of the amplitudes of the sensory components of the response to the first and second impulses of a pair to the response to a single impulse (H1/H and H2/H, respectively). #, ##, ### – p < 0.05, p < 0.01, p < 0.001 differences from the response to a single impulse, **, *** – p < 0.01, p < 0.001 differences between the responses to the first and second impulses of a pair.

Download (204KB)
6. Fig. 5. Examples of mean evoked responses caused by epidural double-pulse stimulation of m. iliacus (IL) and m. vastus lateralis (VL) (interstimulus interval 20 ms; rat #11, segment L2 – responses at current amplitude of 120 μA, segments L4 and L6 – responses at current amplitude of 60 μA); m. gastrocnemius medialis (GM) and m. tibialis anterior (TA) (interstimulus interval 50 ms; rat #45, segment L2 – responses at current amplitude of 120 μA, rat #11, segment L4 – responses at current amplitude of 50 μA, rat #10, segment L6 – responses at current amplitude of 70 μA), dashed line – response to the first stimulus, solid line – response to the second stimulus.

Download (163KB)

Copyright (c) 2024 Russian Academy of Sciences

Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».