Balancing Excitation and Inhibition in the Locomotor Spinal Circuits

Raymond Chia, Chin-Teng Lin
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Abstract

Presynaptic inhibition after spinal cord injury (SCI) has been hypothesised to disproportionately affect flexion reflex loops in locomotor spinal circuitry. Reducing gamma-aminobutyric acid (GABA) inhibitory activity increases the excitation of flexion circuits, restoring muscle activation, and stepping ability. Conversely, nociceptive sensitisation and muscular spasticity can emerge from insufficient GABAergic inhibition. To investigate the effects of neuromodulation and proprioceptive sensory afferents in the spinal cord, a biologically constrained spiking neural network (SNN) was developed. The network describes the flexor motoneuron (MN) reflex loop with inputs from ipsilateral Ia- and II-fibres and tonically firing interneurons. The model was tuned to a baseline level of locomotive activity before simulating an inhibitory-dominant and body-weight supported (BWS) SCI state. Electrical stimulation (ES) and serotonergic agonists were simulated by the excitation of dorsal fibres and reduced conductance in excitatory neurons. ES was applied across all afferent fibres without phase- or muscle-specific protocols. The present study describes, for the first time, the release of GABAergic inhibition on flexor MNs as a potential mechanism underlying BWS treadmill training. The results demonstrate the synaptic mechanisms by which neuromodulatory therapy tunes the excitation and inhibition of ankle flexor MNs during locomotion for smoother and more coordinated movement.
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平衡运动脊髓回路中的兴奋与抑制
脊髓损伤(SCI)后的突触前抑制被认为会对运动脊髓回路中的屈曲反射环路产生不成比例的影响。减少γ-氨基丁酸(GABA)抑制活动可增加屈曲回路的兴奋,恢复肌肉激活和迈步能力。相反,GABA 能抑制不足会导致痛觉过敏和肌肉痉挛。为了研究神经调节和脊髓本体感觉传入的影响,我们开发了一个生物约束尖峰神经网络(SNN)。该网络描述了屈肌运动神经元(MN)反射环路,其输入来自同侧 Ia 和 II-纤维以及音调发射的中间神经元。在模拟抑制主导和体重支持(BWS)的 SCI 状态之前,先将模型调整到运动活动的基线水平。电刺激(ES)和血清素能激动剂是通过兴奋背侧纤维和降低兴奋神经元的传导来模拟的。电刺激适用于所有传入纤维,没有特定的相位或肌肉协议。本研究首次描述了作为 BWS 跑步机训练潜在机制的屈肌 MN 上 GABA 能抑制的释放。研究结果证明了神经调节疗法在运动过程中调整踝关节屈肌MN兴奋和抑制的突触机制,从而使运动更流畅、更协调。
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