Neurostimulation of the Rat Motor System

Authors: Ting, Windsor Kwan-Chun
Advisor: Ethier, Christian
Abstract: This document synthesizes a body of work concerning the nature of neural plasticity and how neurostimulation may be used to improve motor recovery after neurological insult. We begin with general foundational principles in neuroscience, the structure of the nervous and motor systems in humans and rats, and a brief discussion of neurological injury. The topics are broad and covered with the necessary brevity, but provides critical context for the following chapters. In the first paper, we review the fields of neurostimulation across the clinical and basic science domains in the service of stroke as a model disease for neurological injury, framing the field in terms of three different models of plasticity induction. Our central thesis here is that enhanced understanding of the underlying rules of plasticity, accompanied with advances in greater spatiotemporal precision is necessary to move the field of neurostimulation forward. In the second paper we describe a stable, novel step-by-step protocol to assess corticospinal excitability in the awake, freely behaving rodent, and the associated hardware and software platforms that our team has developed for this purpose. A core feature enables corticomotor excitability assessment in a closed-loop, Electromyogram (EMG)-dependent manner, a novel way of increasing consistency during free behavior in untrained animals. This development platform will be of use to neuroscientists interested in assessing the excitability of the nervous system in awake, unrestrained rodents via electrical or optogenetic interrogation, an important intermediary before trials in non-human primates and eventually humans. In the third paper, we used this prototype platform to investigate electrical paired associative stimulation and the role of spike-timing-dependent plasticity in chronically implanted rats, without the influence of anaesthesia. Our focus was on systematically varying the Inter-Stimulus Interval (ISI) between cortical and muscle stimulation in our animal cohort in order to reveal the effect of relative activity timing at both the cortical and spinal levels. We did not observe significant potentiation across all of the stimulus intervals we tested, but instead observed trends towards Long-Term Depression (LTD)-like effects in the short term across most timing conditions. We discuss possible reasons why we observed these results. In the final paper and project currently in progress, we describe early promising work involving optogenetic and electrical neurostimulation, and stroke recovery as a launchpad for future investigations. We conclude with a general discussion and peer into the future, both in the medium term and the long term. The scientific pursuit, both personally and as a field will continue, as it should. Although this work is designed to be read in sequential order, each chapter stands alone. Collectively, the work in this thesis lays the groundwork and argues for a greater understanding of neural plasticity, development of tools to assess it, and study of its practical applications to achieve enhanced motor recovery after neurological injury.
Document Type: Thèse de doctorat
Issue Date: 2022
Open Access Date: 9 May 2022
Permalink: http://hdl.handle.net/20.500.11794/73369
Grantor: Université Laval
Collection:Thèses et mémoires

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