Characterizing Electromyographic Activity During Locomotion in the MitoPark Mouse Model of Parkinson’s Disease Restricted; Files Only

Abstract

Electromyography (EMG) readings that measure electrophysiological activity of muscle are one

way in which we can track changes in neuromuscular activity. These changes can be investigated

in animal models of Parkinson’s disease (PD) and compared to findings in Parkinson’s patients

to shed light on the translational relevance of these animal models in characterizing

neuromuscular changes associated with Parkinson’s disease. The MitoPark (MP) mouse model

of PD mimics the progressive nature of the disease in humans via a knockout of Tfam, a gene

encoding a mitochondrial transcription factor, specifically in dopaminergic neurons. This is

achieved by crossing DAT-Cre mice with Tfam-floxed mice, resulting in mitochondrial

dysfunction, oxidative stress, and dopaminergic neuron death leading to Parkinsonian motor

symptoms.

Potential similarities or differences in electromyographic (EMG) activity between this

mouse model and human Parkinson’s patients have not been well-researched. To address this, we

analyzed gait and EMG patterns of activity in the deltoid and triceps lateral head muscles in

comparison to wildtype (WT) mice across early (16-18 weeks) and late (23-25 weeks) disease

stages during a 15-minute Open Field assay. MP mice showed comparable average body and

paw speeds when compared to WT mice, but with a general decreasing trend from WT to Early

MP to Late MP. When mice locomoting at similar body speeds were compared, we found no

significant differences across groups in percentage of time spent in the swing phase of stepping.

MP mice took significantly fewer steps per recording compared to WT. Step-triggered averaging

(STA) of EMG activity revealed no statistically significant differences in peak STA timing or

STA half-width between WT and MP mice in either muscle, suggesting that the timing and

duration of average muscle activation patterns relative to stepping events may be preserved in

these muscles at the disease stages examined. However, these results should be interpreted with

caution given the small sample sizes of n=2 WT, n=2 late MP, and n=3 early MP mice, and

further recordings will be necessary.

As a preliminary extension of this work, a single-step analysis pipeline was developed to

characterize EMG burst activity at the level of individual stepping events.

Table of Contents

Introduction………………………………………………………………………………………..1

Parkinson’s Disease in Humans……………………………………………………….......1

Rodent Models of Parkinson’s Disease………………………...…………………………2

Methods……………………………………………………………………………………………4

Open Field Behavioral Assay……………………………………………………………..5

Recording Video and EMG Data………………………………………………………….6

EMG/DLC/Gait/Video Reviewer…………………………………………………………7

DeepLabCut Tracking and Video Labeling……………………………………………….7

Gait Analysis………………………………………………………………………………9

Preprocessing of EMG Data……………………………………………………………..10

Evaluating EMG Channel Viability……………………………………………………...11

Step-Triggered Averages Analysis………………………………………………………12

Preliminary Single Step Analysis………………………………………………………..15

Results …………………………………………………………………………………………...16

MP Mice Take Fewer Steps than Wildtype Mice ……………………………………….17

MP Mice and WT Mice Locomote at Similar Speeds…………………………………...21

At Comparable Body Speeds, MP and WT Mice Spend Similar Amounts of Time in the

Swing Phase of Locomotion…………………………………………………………….21

Peak STA Timing Does Not Differ Between MP and WT Mice……………………….24

STA Half-Widths Do Not Differ Between MP and WT Mice……………………….…27

Preliminary Single-Step Analysis……………………………………………………….29

Burst Extraction Examples………………………………………………………………32

Discussion……………………………………………………………………………………….34

Limitations……………………………………………………………………………………….35

Future Directions………………………………………………………………………………...37

Works Cited……………………………………………………………………………………...38

About this Honors Thesis

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, General Biology, Neuroscience
Keyword	Open Field electromyography Parkinson's disease Locomotion EMG MitoPark
Committee Chair / Thesis Advisor	Dieter Jaeger, Emory University
Committee Members	Thomas Wichmann, Emory University Samuel Sober, Emory University

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