Author ORCID Identifier

https://orcid.org/0000-0001-8323-079X

Date of Award

Fall 12-13-2021

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience Institute

First Advisor

Gennady Cymbalyuk

Abstract

We discovered a variety of mechanisms by which a central pattern generator (CPG) can produce multiple qualitatively different bursting rhythms, including steady-state continuous bursting, transient fast bursting, and episodic bursting. We investigated whether the mammalian locomotion CPG is multifunctional, producing more than one functional rhythm. We constructed computational Hodgkin-Huxley style models to simulate the cat locomotion CPG and the mouse locomotion CPG. Each of these models was constructed as a half-center oscillator (HCO), a network constituted by two neural populations that reciprocally inhibit one another. We used cellular dynamics as opposed to synaptic dynamics to generate multiple function rhythms. In the case of cat locomotion, our previously published model generated multistability of the locomotion rhythm (1 Hz) and the paw-shaking rhythm (10 Hz). This was the first model to be able to produce multistability of two rhythms with frequencies that differ by an order of magnitude. We also demonstrated that this model produces transient paw-shake-like activity when perturbed by a pulse of current that represents sensory input to the CPG. We compared this transient model activity to experimental recordings of EMG activity in the cat hindlimb during paw-shake responses that occurred while the cat was walking. In the case of mouse locomotion, we constructed a model that produces both continuous bursting and episodic bursting, in which the model can transition from one to the other by a slight modulation of parameters. We compared model activity to experimental electrophysiological recordings from motor neurons in the isolated neonatal mouse spinal cord under various pharmacological conditions. In both cases, our model simulated key characteristics of the rhythms in question.

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