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Assessment of Spontaneous Locomotor and Running Activity in Mice

互联网2013-12-31

1732

Abstract
Table of Contents
Materials
Figures
Literature Cited

Abstract

The locomotor activity of laboratory mice is a global behavioral trait which can be valuable for the primary phenotyping of genetically engineered mouse models as well as mouse models of pathologies affecting the central and peripheral nervous systems, the musculoskeletal system, and the control of energy homeostasis. Basal levels of mouse locomotion can be recorded using infrared monitoring of movements, and further information can be gathered by giving the animal access to a running wheel, which will greatly enhance its spontaneous physical activity. Described here are two detailed protocols to evaluate basal locomotor activity and spontaneous wheel running. Curr. Protoc. Mouse Biol. 1:185?198. © 2011 by John Wiley & Sons, Inc.

Keywords: activity; locomotion; wheel running; training

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Introduction
Basic Protocol 1: Assessment of Spontaneous Locomotor Activity Using Infrared Detection
Basic Protocol 2: Assessment of Spontaneous Running Activity in Wheels
Commentary
Literature Cited
Figures

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Materials

Basic Protocol 1: Assessment of Spontaneous Locomotor Activity Using Infrared Detection

Materials

Mice (e.g., C57BL/6J)
Housing room dedicated to this experiment with restricted access of lab personnel during recording
Locomotor activity monitoring system (see Fig. ): e.g., TSE (http://www.tse‐systems.com/), Columbus Instruments (http://www.colinst.com/), or PanLab (http://www.panlab.com/), typically composed of several of the following units:
- Cage for single mouse housing (with a design and feeding/drinking systems as close as possible to the home cage)
- Infrared transmitters and receivers for horizontal movement in x direction
- Infrared transmitters and receivers for horizontal movement in y direction (optional)
- Infrared transmitters and receivers for vertical movement in z direction (rearings)
- Food and water consumption monitoring devices (optional, allows correlation of activity with feeding/drinking patterns)

NOTE: The position of all infrared transmitters and receivers should be adjustable, and the inter‐beam spacing is typically on the order of 1 to 3 cm. Figure provides an example of a home‐cage monitoring system (Fig. A) and of a metabolic cage including actimetry infrared beams (Fig. B). Ideally, home‐cage monitoring is the preferred option, as the presence of bedding and a familiar environment minimizes the stress induced by a change of housing conditions. However, metabolic cages can offer advantages such as the ability to measure energy expenditure and to collect urine and feces. NOTE: A computer and software supplied by the manufacturer of the system are required to quantify beam breaks and process the data. Each system has specificities in terms of data processing, but general considerations are addressed in steps 11 and 12, below.

Basic Protocol 2: Assessment of Spontaneous Running Activity in Wheels

Materials

Mice (e.g., C57BL/6J)
Housing room dedicated to this experiment with restricted access of lab personnel during recording
Cages with free running wheels and food/water supply: e.g., Lafayette (http://www.lafayetteinstrument.com/), PanLab (http://www.panlab.com/), TSE (http://www.tse‐systems.com/), Tecniplast (http://www.tecniplast.it/); Figure shows two examples of typical setups—the wheel diameter is variable depending on the manufacturer but should be ∼12 to 30 cm, and wheels should be equipped with a system to quantify the number of revolutions
Computer and software supplied by the manufacturer of the system to quantify the number of revolutions as a function of time

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Figures

Figure 1. Schematic representation of an infrared‐based activity monitoring cage.

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Figure 2. Example of systems for locomotor activity measurements in home cages (A ) and in metabolic cages (B ). The home‐cage monitoring system (supplied by TSE) monitors horizontal activity in both directions ( x and y ) as well as vertical activity ( z ), whereas the metabolic cages (CLAMS, Columbus Instruments) measure vertical activity and horizontal activity in only one direction ( x ). Both systems integrate different technologies to measure feeding and drinking behavior in real time. Note that the overall design of the home cage system (bedding, feeding/drinking systems) is closer to usual mouse housing cages, but metabolic cages also allow measuring indirect calorimetry and collecting urine and feces.

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Figure 3. Example of cages used to record spontaneous wheel running. (A ) A system from Lafayette Instruments, and (B ), a system from Tecniplast/Bioseb. Both systems integrate computer‐controlled recording of the number of wheel revolutions.

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Figure 4. The levels of locomotor activity in the three dimensions are correlated. The locomotor activity of wild‐type mice on different genetic backgrounds (C57BL/6J and DBA2/J ) and under different dietary challenges (chow diet and high‐fat diet for 12 weeks) was measured over 24 hr using home‐cage monitoring on the TSE setup described in Fig. 2A, with a 12 hr:12 hr dark:light period. The total beam breaks and distance covered during the light and dark phases were determined, and horizontal activity in the two dimensions was compared (A ), and correlated to the distance traveled (B ), and to vertical locomotor activity (C ).

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Figure 5. Horizontal and vertical locomotor activity of unchallenged or obese wild‐type mice in home cages. The locomotor activity of wild‐type male C57BL/6J mice fed chow diet (CD) or high‐fat diet (HFD) for 12 weeks ( n = 4/group) was measured over 24 hr using home‐cage monitoring on the TSE setup described in Fig. 2A, with a 12 hr:12 hr dark:light period. Panels A and C represent the circadian activity counts with integration of the data over 1‐hr periods, while panels B and D represent the same data integrated over the 12 hr of the light and dark phases, or over 24 hr (total). Data are represented as mean ± SEM and * represents a statistical significant difference ( p < 0.05) using a 1‐way ANOVA followed by a Bonferroni test.

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Figure 6. Horizontal and vertical locomotor activity of unchallenged or obese wild‐type mice in metabolic cages. The locomotor activity of wild‐type male C57BL/6J mice described in Figure 5 was measured over 24 hr using metabolic monitoring on the Columbus Instruments CLAMS setup described in Fig. 2B, after a 24‐hr familiarization to the new cage environment. Activity counts were integrated over 1‐hr intervals (A ‐C ), while feeding and drinking behavior was integrated over 2‐hr periods (D ). Data are represented as mean ± SEM and * represents a statistical significant difference ( p < 0.05) using a 1‐way ANOVA followed by a Bonferroni test.

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Figure 7. The locomotor activity measured in home cages and metabolic cages is correlated. Results from Figures and were integrated over the 12 hr of the (A ) light and (B ) dark phases, and Xtot counts measured in metabolic cages was plotted against x + y counts measured in home cages.

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Figure 8. Profiles of spontaneous wheel running over 24 hr (A ) and 2 weeks (B ). 10 wild‐type male C57BL/6J mice of 12 weeks of age were housed in cages with free access to a running wheel as described in Fig. 3A. Panel A represents a typical circadian wheel running pattern while panel B represents the average distance covered daily over 2 weeks. Data are represented as mean ± SEM.

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Figure 9. A training period consisting of 2 weeks of wheel running enhances exercise performance in a treadmill test. At the end of the 2‐week wheel‐running period, trained mice from Figure 8 were compared to sedentary matched controls that had been housed in similar cages without access to a wheel, using endurance (long moderate‐intensity) tests (A ) and power (short high‐intensity) treadmill performance tests (B ) as described in Marcaletti et al. (). Data are represented as mean ± SEM and * represents a statistical significant difference ( p < 0.05) using a 1‐way ANOVA followed by a Bonferroni test.

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Literature Cited

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