Chemogenetic modulation of sensory afferents induces locomotor changes and plasticity after spinal cord injury.
Chemogenetic modulation of sensory afferents induces locomotor changes and plasticity after spinal cord injury.
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DOI：
10.3389/fnmol.2022.872634
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发表时间：
2022
影响因子：
4.8
通讯作者：
Spence, Andrew J.
中科院分区：
文献类型：
--
作者：
Eisdorfer, Jaclyn T.;Sobotka-Briner, Hannah;Schramfield, Susan;Moukarzel, George;Chen, Jie;Campion, Thomas J.;Smit, Rupert;Rauscher, Bradley C.;Lemay, Michel A.;Smith, George M.;Spence, Andrew J.
关键词：
治疗脊髓损伤(SCI)的神经调节疗法，如硬膜外电刺激(EES)，在改善患者预后方面日益有效。这些改善被认为至少部分归因于神经元回路的可塑性。确切地说，哪些回路受到影响，哪些传入类在刺激变化方面最有效，这些仍然是重要的悬而未决的问题。基因工具，如由设计药物(DREADD)专门激活的设计受体(DREADD)，支持靶向和可逆的神经调节以及操纵神经元的组织学特征。因此，我们用兴奋性(HM3Dq)DREADDS对大鼠腰椎大直径外周传入进行转导和激活，以类似于EES的方式，在大鼠半横断模型中开始追踪可塑性并观察伴随的运动变化。与对照组动物相比，慢性DREADDS激活加上每周三次跑步机训练，可以增加运动池和Clarke‘s柱内的传入荧光标记。这种可塑性可能是我们在不同恢复阶段观察到的运动学差异的基础，包括DREADDS动物后躯高度增加和变化较少、步幅持续时间较短、恢复早期踝关节更弯曲、摆动阶段踝关节角度变化较小，但髋关节角度变化更大。停用DREADDS激动剂氯氮平-N-氧化物(CNO)后，这些运动学差异基本不受影响；这表明DREADDS的激活在以后的恢复过程中不是必需的。然而，我们在没有CNO激活的DREADDS动物中观察到了间歇性的“屈曲”现象，这种现象在CNO重新给药时不会发生。未来的研究可以使用更精确的特定传入类别的基因靶点，并利用肌肉记录来找出传入调制在改变运动输出方面最有影响的地方。
Neuromodulatory therapies for spinal cord injury (SCI) such as electrical epidural stimulation (EES) are increasingly effective at improving patient outcomes. These improvements are thought to be due, at least in part, to plasticity in neuronal circuits. Precisely which circuits are influenced and which afferent classes are most effective in stimulating change remain important open questions. Genetic tools, such as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), support targeted and reversible neuromodulation as well as histological characterization of manipulated neurons. We therefore transduced and activated lumbar large diameter peripheral afferents with excitatory (hM3Dq) DREADDs, in a manner analogous to EES, in a rat hemisection model, to begin to trace plasticity and observe concomitant locomotor changes. Chronic DREADDs activation, coupled with thrice weekly treadmill training, was observed to increase afferent fluorescent labeling within motor pools and Clarke's column when compared to control animals. This plasticity may underlie kinematic differences that we observed across stages of recovery, including an increased and less variable hindquarters height in DREADDs animals, shorter step durations, a more flexed ankle joint early in recovery, a less variable ankle joint angle in swing phase, but a more variable hip joint angle. Withdrawal of DREADDs agonist, clozapine-N-oxide (CNO) left these kinematic differences largely unaffected; suggesting that DREADDs activation is not necessary for them later in recovery. However, we observed an intermittent “buckling” phenomenon in DREADDs animals without CNO activation, that did not occur with CNO re-administration. Future studies could use more refined genetic targeted of specific afferent classes, and utilize muscle recordings to find where afferent modulation is most influential in altering motor output.
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影响因子：
5.4
作者：
Akache, Bassel;Grimm, Dirk;Kay, Mark A.
通讯作者：
Kay, Mark A.
影响因子：
5.3
作者：
Kelamangalath, Lakshmi;Tang, Xiaoqing;Bezik, Kathleen;Sterling, Noelle;Son, Young-Jin;Smith, George M.
通讯作者：
Smith, George M.
脊髓刺激必须保留本体感受，以使脊髓损伤的人类运动。
影响因子：
25
作者：
Formento E;Minassian K;Wagner F;Mignardot JB;Le Goff-Mignardot CG;Rowald A;Bloch J;Micera S;Capogrosso M;Courtine G
通讯作者：
Courtine G
影响因子：
5.3
作者：
Arvanian, Victor L.;Schnell, Lisa;Lou, Li;Golshani, Roozbeh;Hunanyan, Arsen;Ghosh, Arko;Pearse, Damien D.;Robinson, John K.;Schwab, Martin E.;Fawcett, James W.;Mendell, Lorne M.
通讯作者：
Mendell, Lorne M.
DOI：
10.1111/j.1748-1716.1983.tb07267.x
发表时间：
1983-01-01
期刊：
ACTA PHYSIOLOGICA SCANDINAVICA
影响因子：
--
作者：
ANDERSSON, O;GRILLNER, S
通讯作者：
GRILLNER, S