Department of Integrative Biology and Physiology, University of California, Los Angeles, California.
Neuroscience Department, International School for Advanced Studies (SISSA), Trieste, Italy.
J Neurophysiol. 2021 Nov 1;126(5):1635-1641. doi: 10.1152/jn.00278.2021. Epub 2021 Oct 13.
In intact and spinal-injured anesthetized animals, stimulation levels that did not induce any visible muscle twitches were used to elicit motor evoked potentials (MEPs) of varying amplitude, reflecting the temporal and amplitude dynamics of the background excitability of spinal networks. To characterize the physiological excitability states of neuronal networks driving movement, we designed five experiments in awake rats chronically implanted with an epidural stimulating interface, with and without a spinal cord injury (SCI). First, an uninjured rat at rest underwent a series of single electrical pulses at sub-motor threshold intensity, which generated responses that were continuously recorded from flexor and extensor hindlimb muscles, showing an intrinsic patterned modulation of MEPs. Responses were recruited by increasing strengths of stimulation, and the amplitudes were moderately correlated between flexors and extensors. Next, after SCI, four awake rats at rest showed electrically induced MEPs, varying largely in amplitude, of both flexors and extensors that were mainly synchronously modulated. After full anesthesia, MEP amplitudes were largely reduced, although stimulation still generated random baseline changes, unveiling an intrinsic stochastic modulation. The present five cases demonstrate a methodology that can be feasibly replicated in a broader group of awake and behaving rats to further define experimental treatments involving neuroplasticity. Besides validating a new technology for a neural stimulating interface, the present data support the broader message that there is intrinsic patterned and stochastic modulation of baseline excitability reflecting the dynamics of physiological states of spinal networks. Chronic implants of a new epidural stimulating interface trace dynamics of spinal excitability in awake rats, before and after injury. Motor evoked potentials induced by trains of pulses at sub-motor threshold intensity were continuously modulated in amplitude. Oscillatory patterns of amplitude modulation reduced with increasing strengths of stimulation and were replaced by an intrinsic stochastic tone under anesthesia. Variability of baseline excitability is a fundamental feature of spinal networks, affecting their responses to external input.
在完整和脊髓损伤麻醉动物中,使用不会引起任何可见肌肉抽搐的刺激水平来引出运动诱发电位(MEPs),其幅度反映了脊髓网络背景兴奋性的时间和幅度动态。为了描述驱动运动的神经元网络的生理兴奋性状态,我们在慢性植入硬膜外刺激接口的清醒大鼠中设计了五个实验,既有脊髓损伤(SCI),也有脊髓损伤。首先,在休息状态下,一只未受伤的大鼠接受了一系列亚运动阈值强度的单电脉冲刺激,这些刺激产生的反应从屈肌和伸肌后肢肌肉中连续记录下来,显示出 MEPs 的固有模式调制。通过增加刺激强度来募集反应,并且屈肌和伸肌之间的幅度具有中度相关性。接下来,在 SCI 后,四名休息状态下的清醒大鼠表现出电诱导的 MEPs,其幅度变化很大,屈肌和伸肌的反应主要同步调制。在完全麻醉后,MEP 幅度大大降低,尽管刺激仍然产生随机的基线变化,揭示了固有随机调制。这五个案例展示了一种可以在更广泛的清醒和行为大鼠群体中复制的方法,以进一步定义涉及神经可塑性的实验治疗。除了验证一种新的神经刺激接口技术外,本数据还支持更广泛的信息,即基线兴奋性存在固有模式和随机调制,反映了脊髓网络生理状态的动态。慢性植入新型硬膜外刺激接口可在损伤前后追踪清醒大鼠脊髓兴奋性的动态。在亚运动阈值强度的脉冲串刺激下诱导的运动诱发电位在幅度上连续调制。随着刺激强度的增加,幅度调制的振荡模式减少,并在麻醉下被固有随机音调所取代。基线兴奋性的可变性是脊髓网络的一个基本特征,影响其对外部输入的反应。
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