Tracking Individual Running Metrics in Mice Using a Voluntary Wheel Running Protocol that Minimizes Social Isolation

Summary

This protocol describes an effective voluntary wheel-running model that can be implemented in various research contexts. Unlike other voluntary running models, this method avoids isolation housing while tracking running metrics in individual mice.

Abstract

Voluntary wheel running (VWR) in rodents is used to evaluate performance and endurance and to simulate exercise. In contrast to other exercise paradigms that require aversive stimulus to induce active movement, wheel running is voluntary. VWR generally consists of placing a running wheel inside the mouse home cage. However, analyzing exercise parameters can typically only be conducted when mice are individually housed, while overall cage effects can be reported when mice are group-housed. Therefore, the current models force experimenters to choose between measuring individual exercise parameters in single-housed mice or measuring group effects in group-housed mice; depending on the research question and model, this could be limiting.

Therefore, the goal of this method is to demonstrate a protocol that assesses VWR in a mouse model by quantifying running parameters in individual mice, with minimal isolation. We report on device design, preoperative preparations, and experiment setup. Results of a 6-week training protocol using this VWR model suggest it provides sufficient stimulus to increase spatial object recognition memory, comparable to the clinical effect of exercise. This simple and inexpensive model facilitates investigation into the effect of VWR on multiple measurements of wheel activity, minimizing factors that could limit or affect experimental outcomes.

Introduction

Exercise beneficially impacts physiological and psychological health and can improve the pathophysiology of numerous diseases¹. Physical activity is critical for health span, and World Health Organization (WHO) reported in 2020 that increasing physical activity reduces the risk of numerous diseases, including psychological disorders². In addition to disease prevention, exercise can enhance brain function by stimulating blood flow³, inducing neurogenesis, particularly in the hippocampus⁴, a key brain region for learning and memory, hormonal regulation⁵

Protocol

All experimental procedures were approved by Rowan University's Animal Care and Use Committee. Male mice weighed between 20 g and 27 g and were 8-10 weeks old at the start of the study. Mice were housed in groups of 4, in a controlled environment (12:12 h light/dark cycle) with ad libitum access to food and water.

1. Wheels setup

1. On the outer middle circumference of each wheel, glue one magnet. This magnet will be detected by the censor of the speedometer to monitor VWR (Figure 1A).
2. On the opposite side of the wheel, glue an object of similar weight to the magnet ....

Results

In this study, 20 C57BL/6 male mice were randomly assigned to one of the two groups: no-exercise (NO-EX) or exercise (VWR) for 6 weeks. Individual running parameters were recorded daily on speedometers and plotted below ± SEM (Figure 3A-C). Throughout the 6 weeks, mice were most active in week 2, during which they spent on average 2,135.87 ± 351.14 s on the wheel, traveling a distance of 1.16 ± 0.25 km at a speed of 2.25 ± 0.14 km/h. In contrast, the lowest VWR parameters we.......

Discussion

Various exercise paradigms are used by researchers to evaluate physical activity and its effects in rodents, including voluntary and forced running paradigms. Compared to the forced exercise paradigms, VWR allows mice to freely run at a lower intensity, which minimizes stressful conditions²². Currently, investigators can collect exercise parameters of individual mice by single-housing them^23,24,25,

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
ANY-box 5-Behavior Test System	Stoelting	65000	https://stoeltingco.com/Neuroscience/ANY-box-Multi-Configuration-Behavior-Apparatus~9838
Bike Computer Bicycle Wired Speedometers and Odometers	IPSXP	N/A	Any wired speedometer that meausre distsnce, time, speed could work
Clear Adhesive Protective Liner	Con-Tact Brand	N/A	https://con-tactbrand.com/products/clear-cover%E2%84%A2-clear-matte?_pos=1&_fid=be2dc000c&_ss=c
GraphPad Prism
Instant Adhesive 496 Super Bonder	Loctite	S-24546	https://www.uline.com/Product/Detail/S-24546/Adhesives-Glue-Epoxy/Loctite-Instant-Adhesive-496-Super-Bonder?pricode=WB0948&gadtype=pla&id= S-24546&gad_source=1&gclid=Cjw KCAjw68K4BhAuEiwAylp3klS0FN Ur-l_xKkue1NUmruDDV48QO5b2tVH W9Bc08s9eZKmedj-yxBoCgIEQAvD_BwE
Pro Mag Neodymium Magnet	Applied Magnets	ND018-6	If choosing other magnets, make sure they are strong enough to be detected by the censor
Silent Spinner Small Animal Exercise Wheels (mini 11.4 cm)	Kaytee	SKU# 100079369	https://www.kaytee.com/all-products/ small-animal/silent-spinner-wheel
White Foam Boards	Pacon	5553	https://pacon.com/foam-board-350/pacon-foam-board-20-x-30-white-10pkg-2.html