An epidural stimulating interface unveils the intrinsic modulation of electrically motor evoked potentials in behaving rats

• Published in: Journal of neurophysiology Vol. 126; no. 5; pp. 1635 - 1641
• Main Authors: Taccola, Giuliano, Culaclii, Stanislav, Zhong, Hui, Gad, Parag, Liu, Wentai, Edgerton, V Reggie
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.11.2021
• Series: Spinal Networks and Spinal Cord Injury: A Tribute to Reggie Edgerton
• Subjects: Anesthesia; Animals; Behavior, Animal - physiology; Case Studies in Neuroscience; Disease Models, Animal; Electromyography; Evoked Potentials, Motor - physiology; Nerve Net - physiology; Rats; Spinal Cord - physiology; Spinal Cord Injuries - physiopathology; Spinal Cord Stimulation; neuromodulation; spinal cord; multielectrode array; chronic injury; awake animal
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.00278.2021

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.