Tests to assess motor phenotype in mice: a user's guide

Key Points

  • The identification of motor abnormalities in mouse models of disease is dependent on the choice of an appropriate behavioural test(s).

  • The utility of a given test is dependent on its validity with respect to the disease model being studied, its reliability and its sensitivity.

  • The simplest tests involve neurological scales based on observational ratings, such as those in the SHIRPA protocols or the cylinder test.

  • Gross aspects of motor behaviour such as general locomotor activity can be measured through the use of open-field locomotion or home cage wheel running tests.

  • More refined motor function can be evaluated by determining manual dexterity, as assessed in a range of reaching and food manipulation tasks, such as the staircase or paw reaching tests.

  • Motor coordination and balance can be measured with a rotarod, in climbing and swimming tasks or in beam walking or stepping tests.

  • Gait abnormalities can be identified through the footprint test.

  • The most complex aspects of skilled motor performance and habit formation are best assessed using operant motor learning tasks, such as the five-choice serial reaction time and the serial implicit learning tasks.

  • Prepulse inhibition is a unique test of the cognitive–motor interface in which attention to brief warning stimuli attenuates the effect of unpredictable acoustic stimuli on the startle reflex.

  • Equipment can vary in complexity and cost. In many cases simple, low-tech equipment may be used.

Abstract

The characterization of mouse models of human disease is essential for understanding the underlying pathophysiology and developing new therapeutics. Many diseases are often associated with more than one model, and so there is a need to determine which model most closely represents the disease state or is most suited to the therapeutic approach under investigation. In the case of neurological disease, motor tests provide a good read-out of neurological function. This overview of available motor tasks aims to aid researchers in making the correct choice of test when attempting to tease out a transgenic phenotype or when assessing the recovery of motor function following therapeutic intervention.

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Figure 1: A selection of behavioural tests for mice.
Figure 2: Rates of progression of neurological impairment and onset of phenotype.
Figure 3: Serial choice responding in the SILT operant task.

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Acknowledgements

Work from the authors' laboratory has been funded by the Medical Research Council, the Biotechnology and Biological Sciences Research Council, the Cure Huntington's Disease Initiative, the Hereditary Disease Foundation and the European Union Seventh Framework programme.

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Simon P. Brooks and Stephen B. Dunnett

Tests to assess motor phenotype in mice: a user's guide. Nature Reviews Neuroscience 10 (2005); doi:10.1038/nrn2652

Stephen B. Dunnet receives a royalty from Campden Instruments UK on sales of the staircase test apparatus.

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Related links

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DATABASES

OMIM

Huntington's disease

Parkinson's disease

FURTHER INFORMATION

Stephen B. Dunnett's homepage

MRC Harwell web page on SHIRPA

Glossary

6-OHDA

A neurotoxin that is selective for catecholamine neurons and is widely used to produce an animal model of Parkinson's disease following injection into the nigrostriatal dopamine pathway.

L-DOPA

The biochemical precursor to the neurotransmitter dopamine. It is used as a therapeutic drug for dopamine replacement therapy in Parkinsons disease.

Time bin

Subdivision of an experimental time period, the use of which enhances a test's sensitivity.

Operant tasks

Behavioural tests based on the principles of 'operant' (or instrumental) learning theory, in which the experimental subject makes voluntary responses of a specified type or timing to obtain a reward or to avoid punishment. The testing is typically conducted in automated apparatus, known as operant chambers.

Implicit learning

Learning that occurs without the explicit awareness of the learner. The classic example of this is a child's learning of the syntax and rules of language before schooling.

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Brooks, S., Dunnett, S. Tests to assess motor phenotype in mice: a user's guide. Nat Rev Neurosci 10, 519–529 (2009). https://doi.org/10.1038/nrn2652

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