– collect and analyze data from both with the same instrumentation, thanks to DigiGait!

There is some debate about treadmill walking vs. overground “voluntary” walking for gait analysis of animal models of human diseases. Vendors that offer only solutions for overground walking seem to emphasize that the “voluntary” paradigm, in which the animal may or may not traverse a walkway at an unknown speed, is better than the treadmill paradigm, during which the animal is compelled to walk on a treadmill at speeds and inclines prescribed by the researcher for a very brief period of time [a few seconds typically]. What’s the difference? How does the selection of gait analysis technique affect my research?

With voluntary walking, the animal, usually a mouse or rat, is given the task to walk through a tunnel or over an edge-lit illuminated walkway. See Video 1 for an example of this. It is the hope of the researcher that the animal will actually walk across the walkway. It is also the hope of the researcher that the animal walks continuously, does not stop, or turn around and go the reverse direction.

The researcher also hopes that the animals from a study will all walk the same speed [the researcher knows that if the animals walk different speeds that the findings about differences in gait are likely due to the differences in speed].

Since the walkway length is practically only sufficient for a few steps, it is also the hope of the researcher that the animals repeat the test in a somewhat similar fashion, in order to generate enough strides for statistical analyses.  Some vendors, in order to give some hope to the researchers that the animals will cooperate, provide a goal box or a reward center for the animals. It becomes clear, then, that the researchers’ hopes for success of overground voluntary gait analysis are based on the whims of the animals

Lateral View of Running Mouse Pup from Baxter Thomas on Vimeo.

From a purveyor of technology similar to the MouseWalk Freestyle module. Note the exploratory and intermittent walking of the subject. In this case, it is almost impossible to quantify the gait. Rather, the video conveys only the “intermittent” and “exploratory” aspects of its movement.

In sharp contrast, the treadmill paradigm empowers the researchers to conduct their experiments to readily and repeatedly obtain definitive gait data under tightly controlled conditions. Whereas the voluntary overground paradigm gives control of the success of the experiment to the animal, the treadmill paradigm arms the researcher with a Standard Operating Procedure [SOP] for the team [researchers and animals] to follow to fully analyze the gait under a wide range of conditions [slow speed, fast speed, voluntary walking speeds, up an incline, down a decline]. The SOP for mice with ALS might be different than the SOP for hamsters with muscular dystrophy.

But the researchers decide the protocols, based on science and the literature and the human correlates, designing a gait analysis protocol with the likelihood of discovering definitive answers about motor abnormalities in the animal models, independent of what the animals might do voluntarily. With treadmill walking, the animal is simply placed on a motorized treadmill [initially set to zero speed]. The speed of walking can then be dictated by the researcher; perhaps a slow walking speed for clearly compromised mice, or fast challenging speeds for subtle phenotypes or early evidence of a motor problem. The treadmill is switched on, the treadmill belt commences moving, and the animal walks!

Since mice and rats recruit their limbs quite quickly, the duration of the test is usually short, maybe 5 seconds or so. That’s it! The animal is placed back into its cozy cage, and via DigiGait Imaging System, the researcher has a movie of the ventral plane of the subject during its walking, from which numerous metrics of posture and locomotion are extracted.

All of the animals can sequentially be introduced to the treadmill, and walk the same speed for the same amount of time.   During a typical study, 10 mice can be studied in < 30 minutes.   With the DigiGait treadmill paradigm, there is no “hoping” for the success of the study. Rather, the researcher has a protocol and executes the protocol – data sought, data generated.

Recognizing that in some instances it may be useful to have data from the overground paradigm in addition to the treadmill data, the DigiGait system offers both within its basic footprint. The MouseWalk Freestyle companion compartment enables the subject to walk voluntarily. (see Video 2).  This module has been useful in several peer reviewed publications, including a study of a mouse model of amyotrophic lateral sclerosis [1], a model of Down syndrome [2], and a model of ethanol-intoxication [3]. Of course, since the DigiGait Ventral Plane Videography software can analyze the gait of the subjects walking numerous strides, the software is also applicable to the study of the subject walking overground voluntarily. These data might be useful to help design the treadmill protocol.

For example, if a preferred voluntary speed is determined via the MouseWalk Freestyle studies, it might be interesting to use that speed for the treadmill study, in order to ensure that all of the animals within the study group walk the same speed, since differences in walking speed are the most important confounder in the interpretation of gait. Another application of MouseWalk Freestyle is for animals that are simply too dysfunctional to walk on the treadmill. MouseWalk may yet be able to describe interesting aspects about the animal’s kinematics

MouseWalk Freestyle from Baxter Thomas on Vimeo.

Mouse walking voluntarily across the MouseWalk Freestyle.

The DigiGait Imaging System, with the MouseWalk Freestyle Bundle, provides the researcher to examine treadmill and voluntary overground walking and running.

DigiGait – data sought, data generated!

References:

1. Vinsant S, Mansfield C, Jimenez-Moreno R, Del Gaizo Moore V, Yoshikawa M, Hampton TG, Prevette D, Caress J, Oppenheim RW, Milligan C. Characterization of early pathogenesis in the SOD1(G93A) mouse model of ALS: part II, results and discussion. Brain Behav. 2013 Jul;3(4):431-57.
2. Hampton TG, Stasko MR, Kale A, Amende I, Costa AC. Gait dynamics in trisomic mice: quantitative neurological traits of Down syndrome. Physiol Behav. 2004 Sep 15;82(2-3):381-9.
3. Kale A, Amende I, Meyer GP, Crabbe JC, Hampton TG.   Ethanol’s effects on gait dynamics in mice investigated by ventral plane videography. Alcohol Clin Exp Res. 2004 Dec;28(12):1839-48.Footnote
   *Video from Noldus Catwalk XT