Morphological characterization of spinal respiratory phrenic motoneurons

Junhong ZHANG; Zhi'an HU; Shuancheng REN; Wei XIONG

doi:10.16016/j.2097-0927.202201244

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Morphological characterization of spinal respiratory phrenic motoneurons

Neurosciences | 更新时间：2026-01-09

- Morphological characterization of spinal respiratory phrenic motoneurons
- Journal of Army Medical University Vol. 44, Issue 7, Pages: 611-619(2022)
- 作者机构：
  
  1.400038 重庆，陆军军医大学(第三军医大学): 第一附属医院老年医学与特勤医学科
  2.400038 重庆，陆军军医大学(第三军医大学): 基础医学院生理学教研室，脑与智能研究院
  3.857000 西藏日喀则，陆军第 953 医院急诊医学科
- 作者简介：
- 基金信息：
  
  the Fund for Creative Research Groups of National Natural Science Foundation of China(31921003);the Project of "the Thirteenth Five-Year" National Key R & D Program(2018YFC2000301)
- DOI：10.16016/j.2097-0927.202201244
  CLC： R322.85;R329.3;R322.1
- Received：26 January 2022，
  
  Revised：2022-03-03，
  
  Published：15 April 2022
- 稿件说明：
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Junhong ZHANG, Zhi'an HU, Shuancheng REN, et al. Morphological characterization of spinal respiratory phrenic motoneurons[J]. Journal of Army Medical University, 2022, 44(7): 611-619.
DOI：

Junhong ZHANG, Zhi'an HU, Shuancheng REN, et al. Morphological characterization of spinal respiratory phrenic motoneurons[J]. Journal of Army Medical University, 2022, 44(7): 611-619. DOI： 10.16016/j.2097-0927.202201244.

摘要

目的

研究脊髓呼吸相关的膈运动神经元的空间分布位置并比较其与三角肌运动神经元和肋间运动神经元的分布特点差异。

方法

采用从外周到中枢的逆行示踪研究策略，在成年小鼠(

=3)同侧膈肌、三角肌、肋间肌微量注射霍乱毒素β亚基(cholera toxin β-subunit，CTB)或伪狂犬病毒(pseudorabies virus，PRV)，逆行标记支配目标肌肉的脊髓运动神经元，并进一步分析、比较不同脊髓运动神经元的分布特征。

结果

CTB和PRV介导的逆行示踪结果显示：成年小鼠膈运动神经元分布在颈髓C3~C6节段前角Ph9区域，且上述两种逆行示踪剂标记膈运动神经元的效率差异无统计学意义。与C5~C6节段的非呼吸相关的三角肌运动胆碱能神经元相比，膈运动神经元分布在同一脊髓节段前角更腹内侧的位置。与胸髓呼吸相关的肋间运动神经元相比，两组神经元分别在颈髓和胸髓中均沿头-尾轴呈束状纵柱形分布，但膈运动神经元在C3~C6节段细胞数量分布相对均一，而肋间运动神经元在T1~T11节段神经元数目变异较大(

0.000 1)。此外，膈运动神经元分布沿头-尾轴逐渐向脊髓前角内侧偏移，而

呼吸肋间运动神经元则比较均一地分布在脊髓前角外侧区。

结论

成年小鼠膈运动神经元分布在颈髓的C3~C6节段前角Ph9区域，位于三角肌运动神经元腹内侧，且其分布模式较胸髓肋间运动神经元更为均一。

Abstract

Objective

To study the spatial distribution of respiratory-related phrenic motoneurons within the spinal cord and comparison of their distribution characteristics with those of deltoid motoneurons and intercostal motoneurons.

Methods

Using a retrograde tracing strategy from peripheral to central

cholera toxin β-subunit (CTB) or pseudorabies virus (PRV) was microinjected into the ipsilateral diaphragm

deltoid and intercostal muscles of adult mice (

=3) to retrogradely label the spinal motoneurons innervating the target muscles. Then the distribution characteristics of different spinal motoneurons were analyzed and compared.

Results

The results of CTB- and PRV-mediated retrograde tracing showed that phrenic motoneurons in adult mice were distributed in the Ph9 region in the anterior horn of the C3~C6 segments of the cervical cord

and there was no significant difference in the efficiency of labeling phrenic motoneurons with either retrograde tracer. The phrenic motoneurons were distributed in a more ventral medial location in the anterior horn of the same spinal cord segment compared to the non-respiratory related deltoid motor cholinergic neurons in the C5~C6 segments. In contrast to respiratory-related intercostal motoneurons in the thoracic cord

both sets of neurons were distributed in a longitudinal column along the rostro-caudal axis in the cervical and thoracic cord

respectively. However

phrenic motoneurons were relatively uniformly distributed in the number of cells in segments C3~C6

whereas intercostal motoneurons were more variable in the number of neurons in segments T1~T11 (

0.000 1). In addition

the distribution of phrenic motoneurons was gradually shifted tow

ards the medial anterior horn of the spinal cord along the rostro-caudal axis

whereas respiratory intercostal motoneurons were more uniformly distributed in the lateral anterior horn of the spinal cord.

Conclusion

Phrenic motoneurons in adult mice are distributed in segments C3~C6 of the cervical cord

which are located in the more medial Ph9 region of the anterior horn as compared to non-respiratory related deltoid motoneurons in the cervical cord

and have a more even distribution pattern than respiratory intercostal motoneurons in the thoracic cord.

关键词

Keywords

references

DEL NEGRO C A, FUNK G D, FELDMAN J L. Breathing matters[J]. Nat Rev Neurosci, 2018, 19(6): 351-367. DOI: 10.1038/s41583-018-0003-6.

FOGARTY M J, MANTILLA C B, SIECK G C. Breathing: motor control of diaphragm muscle[J]. Physiology (Bethesda), 2018, 33(2): 113-126. DOI: 10.1152/physiol.00002.2018.

SIECK G C, MANTILLA C B. Effect of mechanical ventilation on the diaphragm[J]. N Engl J Med, 2008, 358(13): 1392-1394. DOI: 10.1056/NEJMe0801226.

LANE M A. Spinal respiratory motoneurons and interneurons[J]. Respir Physiol Neurobiol, 2011, 179(1): 3-13. DOI: 10.1016/j.resp.2011.07.004.

ALVAREZ-ARGOTE S, GRANSEE H M, MORA J C, et al . The impact of midcervical contusion injury on diaphragm muscle function[J ] . J Neurotrauma, 2016, 33(5): 500-509. DOI: 10.1089/neu.2015.4054.

MANTILLA C B, ZHAN W Z, SIECK G C. Retrograde labeling of phrenic motoneurons by intrapleural injection[J]. J Neurosci Methods, 2009, 182(2): 244-249. DOI: 10.1016/j.jneumeth.2009.06.016.

PRAKASH Y S, MANTILLA C B, ZHAN W Z, et al . Phrenic motoneuron morphology during rapid diaphragm muscle growth[J ] . J Appl Physiol (1985), 2000, 89(2): 563-572. DOI: 10.1152/jappl.2000.89.2.563.

RANA S, SIECK G C, MANTILLA C B. Diaphragm electromyographic activity following unilateral midcervical contusion injury in rats[J]. J Neurophysiol, 2017, 117(2): 545-555. DOI: 10.1152/jn.00727.2016.

SMITH JC, ELLENBERGER H H, BALLANYI K, et al . Pre-Bötzinger complex: a brainstem region that may generate respiratory rhythm in mammals[J ] . Science, 1991, 254(5032): 726-729. DOI: 10.1126/science.1683005.

QIU K, LANE M A, LEE K Z, et al . The phrenic motor nucleus in the adult mouse[J ] . Exp Neurol, 2010, 226(1): 254-258. DOI: 10.1016/j.expneurol.2010.08.026.

WEBBER C L Jr, WURSTER R D, CHUNG J M. Cat phrenic nucleus architecture as revealed by horseradish peroxidase mapping[J]. Exp Brain Res, 1979, 35(3): 395-406. DOI: 10.1007/BF00236759.

KESWANI N H, HOLLINSHEAD W H. The phrenic nucleus. Ⅲ. Organization of the phrenic nucleus in the spinal cord of the cat and man[J]. Proc Staff Meet Mayo Clin, 1955, 30(24): 566-577.

GOSHGARIAN H G, RAFOLS J A. The phrenic nucleus of th albino rat: a correlative HRP and Golgi study[J]. J Comp Neurol, 1981, 201(3): 441-456. DOI: 10.1002/cne.902010309.

FOURNIER H D, MERCIER P, MENEI P. Spinal repair of ventral root avulsions after brachial plexus injuries: towards new surgical strategies?[J]. Neuro-Chirurgie, 2006, 52(4): 357-366. DOI: 10.1016/s0028-3770(06)71230-9.

SUNSHINE M D, SUTOR T W, FOX E J, et al . Targeted activation of spinal respiratory neural circuits[J ] . Exp Neurol, 2020, 328: 113256. DOI: 10.1016/j.expneurol.2020.113256.

ZHOLUDEVA L V, QIANG L, MARCHENKO V, et al . The neuroplastic and therapeutic potential of s pinal interneurons in the injured spinal cord[J ] . Trends Neurosci, 2018, 41(9): 625-639. DOI: 10.1016/j.tins.2018.06.004.

LEYRER-JACKSON J M, HOLTER M, OVERBY P F, et al . Accumbens cholinergic interneurons mediate cue-induced nicotine seeking and associated glutamatergic plasticity[J ] . eNeuro, 2021, 8(1): ENEURO.0276-ENEURO.0220.2020. DOI: 10.1523/ENEURO.0276-20.2020.

REN S C, WANG Y L, YUE F G, et al . The paraventricular thalamus is a critical thalamic area for wakefulness[J ] . Science, 2018, 362(6413): 429-434. DOI: 10.1126/science.aat2512.

WATSON C, PAXINOS G, KAYALIOGLU G, et al . The spinal cord[M ] //Atlas of the mouse spinal Cord. San Diego: Academic Press, 2009: 308-379. DOI: 10.1016/B978-0-12-374247-6.50020-1.

CONTE W L, KAMISHINA H, REEP R L. Multiple neuroanatomical tract-tracing using fluorescent Alexa Fluor conjugates of cholera toxin subunit B in rats[J]. Nat Protoc, 2009, 4(8): 1157-1166. DOI: 10.1038/nprot.2009.93.

YAO J W, ZHANG Q C, LIAO X, et al . A corticopontine circuit for initiation of urination[J ] . Nat Neurosci, 2018, 21(11): 1 541-1550. DOI: 10.1038/s41593-018-0256-4.

FANG J T, YANG J T, YANG Y, et al . A novel rat model of brachial plexus injury with nerve root stumps[J ] . J Neurosci Methods, 2018, 295: 1-9. DOI: 10.1016/j.jneumeth.2017.11.004.

DIMARCO A F, SUPINSKI G S, BUDZINSKA K. Inspiratory muscle interaction in the generation of changes in airway pressure[J]. J Appl Physiol, 1989, 66(6): 2573-2578. DOI: 10.1152/jappl.1989.66.6.2573.

HAN J N, GAYAN-RAMIREZ G, DEKHUIJZEN R, et al . Respiratory function of the rib cage muscles[J ] . Eur Respir J, 1993, 6(5): 722-728.

SABOISKY J P, GORMAN R B, DE TROYER A, et al . Differential activation among five human inspiratory motoneuron pools during tidal breathing[J ] . J Appl Physiol (1985), 2007, 102(2): 772-780. DOI: 10.1152/japplphysiol.00683.2006.

SMITH B N, BANFIELD B W, SMERASKI C A, et al . Pseudorabies virus expressing enhanced green fluorescent protein: a tool for in vitro electrophysiological analysis of transsynaptically labeled neurons in identified central nervous system circuits[J ] . Proc Natl Acad Sci USA, 2000, 97(16): 9264-9269. DOI: 10.1073/pnas.97.16.9264..

STANLEY S, PINTO S, SEGAL J, et al . Identification of neuronal subpopulations that project from hypothalamus to both liver and adipose tissue polysynaptically[J ] . Proc Natl Acad Sci USA, 2010, 107(15): 7024-7029. DOI: 10.1073/pnas.1002790107.

HOLLINSHEAD W H, KESWANI N H. Localization of the phrenic nucleus in the spinal cord of man[J]. Anat Rec, 1956, 125(4): 683-699. DOI: 10.1002/ar.1091250403.

VANDEWEERD J M, HONTOIR F, DE KNOOP A, et al . Retrograde neuroanatomical tracing of phrenic motor neurons in mice[J ] . JoVE, 2018(132). DOI: 10.3791/56758.

GIRAUDIN A, CABIROL-POL M J, SIMMERS J, et al . Intercostal and abdominal respiratory motoneurons in the neonatal rat spinal cord: spatiotemporal organization and responses to limb afferent stimulation[J ] . J Neurophysiol, 2008, 99(5): 2626-2640. DOI: 10.1152/jn.01298.2007.

DIMARCO A F, KOWALSKI K E. Activation of inspiratory muscles via spinal cord stimulation[J]. Respir Physiol Neurobiol, 2013, 189(2): 438-449. DOI: 10.1016/j.resp.2013.06.001.

SIECK G C, ROY R R, POWELL P, et al . Muscle fiber type distribution and architecture of the cat diaphragm[J ] . J Appl Physiol Respir Environ Exerc Physiol, 1983, 55(5): 1386-1392. DOI: 10.1152/jappl.1983.55.5.1386.

SUNSHINE M D, GANJI C N, REIER P J, et al . Intraspinal microstimulation for respiratory muscle activation[J ] . Exp Neurol, 2018, 302: 93-103. DOI: 10.1016/j.expneurol.2017.12.014.

LEMON R N. Descending pathways in motor control[J]. Annu Rev Neurosci, 2008, 31: 195-218. DOI: 10.1146/annurev.neuro.31.060407.125547.

RAMÍREZ-JARQUÍN U N, TAPIA R. Excitatory and inhibitory neuronal circuits in the spinal cord and their role in the control of motor neuron function and degeneration[J]. ACS Chem Neurosci, 2018, 9(2): 211-216. DOI: 10.1021/acschemneuro.7b00503.

LASKOWSKI M B, SANES J R. Topographic mapping of motor pools onto skeletal muscles[J]. J Neurosci, 1987, 7(1): 252-260. DOI: 10.1523/jneurosci.07-01-00252.1987.

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