Date on Master's Thesis/Doctoral Dissertation

5-2017

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Anatomical Sciences and Neurobiology

Degree Program

Anatomical Sciences and Neurobiology, PhD

Committee Chair

Magnuson, David

Committee Co-Chair (if applicable)

Whittemore, Scott

Committee Member

Bickord, Martha

Committee Member

Howland, Dena

Committee Member

Mellen, Nicholas

Author's Keywords

spinal cord; locomotion; central pattern generator; interneurons; propriospinal neurons

Abstract

This dissertation is focused on dissecting the functional role of two anatomically-defined pathways in the adult rat spinal cord. A TetOn dual virus system was used to selectively and reversibly induce enhanced tetanus neurotoxin expression in L2 neurons that project to L5 (L2-L5) or C6 (long ascending propriospinal neurons, LAPNs). Results focus on the changes observed during overground locomotion. The dissertation is divided into four chapters. Chapter One is a focused introduction to locomotion, including its broad description, the central mechanisms of its expression, how genetic-based approaches defined these mechanisms, and the limitations in these approaches. It concludes with details of the silencing paradigm used here and a summary of the main findings. Chapter Two describes the functional consequences of silencing L2-L5 interneurons. The focus is on selective disruption of hindlimb coordination during overground locomotion, revealing a continuum from walk to hop. These changes are independent of speed, step frequency, and other spatiotemporal features of gait. Left-right alternation was restored during swimming and stereotypic exploration, suggesting a task-specific role. Silencing L2-L5 interneurons partially uncoupled the hindlimbs, allowing spontaneous shifts in coordination on a step-by-step basis. It is proposed this pathway distributes temporal information for left-right hindlimb alternation, securing effective coordination in a context-dependent manner. Chapter Three focuses on the consequences of silencing LAPNs.Three patterns of interlimb coupling are disrupted: left-right forelimb, left-right hindlimb, and contralateral hindlimb-forelimb coordination. Observed again was a context-dependent continuum from walk-to-hop, irrespective of step frequency, speed, and the salient features that define locomotion. However, instead of spontaneous shifts in coordination as observed from L2-L5 interneuron silencing, the breadth of coupling patterns expressed were maintained on a step-by-step basis. It is proposed that this ascending, inter-enlargement pathway distributes temporal information required for left-right alternation at the shoulder and pelvic girdles in a context-dependent manner. Collectively, these data suggest that L2-L5 interneurons and LAPNs are key pathways that distribute left-right patterning information throughout the neuraxis. The functional role(s) of these pathways are exquisitely gated to the context at hand, suggesting that the locomotor circuitry undergoes functional reorganization thereby endowing or masking the silencing-induced disruptions to interlimb coordination.

Available for download on Sunday, November 12, 2017

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