Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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

Nature Reviews Neuroscience volume 10, pages 519–529 (2009)Cite this article

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.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

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.

References

  1. Nolan, P. M. et al. A systematic, genome-wide, phenotype-driven mutagenesis programme for gene function studies in the mouse. Nature Genet. 25, 440–443 (2000).

    CAS  PubMed  Google Scholar 

  2. Lalonde, R. & Strazielle, C. Spontaneous and induced mouse mutations with cerebellar dysfunctions: behavior and neurochemistry. Brain Res. 1140, 51–74 (2007).

    CAS  PubMed  Google Scholar 

  3. Lalonde, R. & Strazielle, C. Motor performance and regional brain metabolism of spontaneous murine mutations with cerebellar atrophy. Behav. Brain Res. 125, 103–108 (2001).

    CAS  PubMed  Google Scholar 

  4. Triarhou, L. C. Neural Transplantation in Cerebellar Ataxia (Landes, 1997).

    Google Scholar 

  5. McIlwain, K. L., Merriweather, M. Y., Yuva-Paylor, L. A. & Paylor, R. The use of behavioral test batteries: effects of training history. Physiol. Behav. 73, 705–717 (2001).

    CAS  PubMed  Google Scholar 

  6. Carter, R. J. et al. Characterisation of progressive motor deficits in mice transgenic for the human Huntington's disease mutation. J. Neurosci. 19, 3248–3257 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Brooks, S. P., Pask, T., Jones, A. L. & Dunnett, S. B. Behavioural profiles of inbred mouse strains used as transgenic backgrounds. I: motor tests. Genes Brain Behav. 3, 206–215 (2004).

    CAS  PubMed  Google Scholar 

  8. Crawley, J. N. & Paylor, R. A proposed test battery and constellations of specific behavioral paradigms to investigate the behavioral phenotypes of transgenic and knockout mice. Horm. Behav. 31, 197–211 (1997).

    CAS  PubMed  Google Scholar 

  9. Rogers, D. C. et al. Behavioral and functional analysis of mouse phenotype: SHIRPA, a proposed protocol for comprehensive phenotype assessment. Mamm. Genome 8, 711–713 (1997).

    CAS  PubMed  Google Scholar 

  10. Irwin, S. Comprehensive observational assessment: Ia. A systematic, quantitative procedure for assessing the behavioral and physiologic state of the mouse. Psychopharmacologia 13, 222–257 (1968).

    CAS  PubMed  Google Scholar 

  11. Rogers, D. C. et al. Use of SHIRPA and discriminant analysis to characterise marked differences in the behavioural phenotype of six inbred mouse strains. Behav. Brain Res. 105, 207–217 (1999). This study demonstrated the sensitivity of the SHIRPA screen for characterizing different mouse lines.

    CAS  PubMed  Google Scholar 

  12. Schallert, T. & Tillerson, J. L. in Central Nervous System Diseases: Innovative Animal Models from Lab to Clinic (eds Emerich, D. F., Dean, R. L. & Sanberg, P. R.) 131–151 (Humana, Totowa, New Jersey, 2000).

    Google Scholar 

  13. Cenci, M. A. & Lundblad, M. in Animal Models of Movement Disorders (ed. LeDoux, M.) 193–209 (Elsevier, Amsterdam, 2005).

    Google Scholar 

  14. Iancu, R., Mohapel, P., Brundin, P. & Paul, G. Behavioral characterization of a unilateral 6-OHDA-lesion model of Parkinson's disease in mice. Behav. Brain Res. 162, 1–10 (2005). This paper describes the unilateral 6-OHDA model of PD and various behavioural tests that have been used to characterize the lesion effects.

    CAS  PubMed  Google Scholar 

  15. Cenci, M. A., Lee, C. S. & Björklund, A. L-DOPA-induced dyskinesia in the rat is associated with striatal overexpression of prodynorphin- and glutamic acid decarboxylase mRNA. Eur. J. Neurosci. 10, 2694–2706 (1998).

    CAS  PubMed  Google Scholar 

  16. Steece-Collier, K. et al. Embryonic mesencephalic grafts increase levodopa-induced forelimb hyperkinesia in Parkinsonian rats. Mov. Disord. 18, 1442–1454 (2003).

    PubMed  Google Scholar 

  17. Lane, E. L., Winkler, C., Brundin, P. & Cenci, M. A. The impact of graft size on the development of dyskinesia following intrastriatal grafting of embryonic dopamine neurons in the rat. Neurobiol. Dis. 22, 334–346 (2006).

    CAS  PubMed  Google Scholar 

  18. Lundblad, M. et al. Pharmacological validation of a mouse model of L-DOPA-induced dyskinesia. Exp. Neurol. 194, 66–75 (2005).

    CAS  PubMed  Google Scholar 

  19. Santini, E. et al. Critical involvement of cAMP/DARPP-32 and extracellular signal-regulated protein kinase signaling in L-DOPA-induced dyskinesia. J. Neurosci. 27, 6995–7005 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Gold, S. J. et al. RGS9–2 negatively modulates L-3,4-dihydroxyphenylalanine-induced dyskinesia in experimental Parkinson's disease. J. Neurosci. 27, 14338–14348 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Glynn, D., Sizemore, R. J. & Morton, A. J. Early motor development is abnormal in complexin 1 knockout mice. Neurobiol. Dis. 25, 483–495 (2007).

    CAS  PubMed  Google Scholar 

  22. Hickey, M. A. et al. Extensive early motor and non-motor behavioral deficits are followed by striatal neuronal loss in knock-in Huntington's disease mice. Neuroscience 157, 280–295 (2008).

    CAS  PubMed  Google Scholar 

  23. Lin, C. H. et al. Neurological abnormalities in a knock-in mouse model of Huntington's disease. Hum. Mol. Genet. 10, 137–144 (2001).

    CAS  PubMed  Google Scholar 

  24. Mangiarini, L. et al. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87, 493–506 (1996).

    CAS  PubMed  Google Scholar 

  25. Barnéoud, P., Lolivier, J., Sanger, D. J., Scatton, B. & Moser, P. Quantitative motor assessment in FALS mice: a longitudinal study. Neuroreport 8, 2861–2865 (1997).

    PubMed  Google Scholar 

  26. Ma, M., Basso, D. M., Walters, P., Stokes, B. T. & Jakeman, L. B. Behavioral and histological outcomes following graded spinal cord contusion injury in the C57Bl/6 mouse. Exp. Neurol. 169, 239–254 (2001).

    CAS  PubMed  Google Scholar 

  27. de Visser, L., van den Boss, R., Kuurman, W. W., Kas, M. J. & Spruijt, B. M. Novel approach to the behavioural characterization of inbred mice: automated home cage observations. Genes Brain Behav. 5, 458–466 (2006). This paper describes how home cage monitoring systems can be used to produce a detailed analysis of mouse home cage activity.

    CAS  PubMed  Google Scholar 

  28. Menalled, L. B. et al. Early motor dysfunction and striosomal distribution of huntingtin microaggregates in Huntington's disease knock-in mice. J. Neurosci. 22, 8266–8276 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Grusser, C. & Grusser-Cornehls, U. Improvement in motor performance of Weaver mutant mice following lesions of the cerebellum. Behav. Brain Res. 97, 189–194 (1998).

    CAS  PubMed  Google Scholar 

  30. De Leonibus, E. et al. Spatial deficits in a mouse model of Parkinson disease. Psychopharmacology (Berl.) 194, 517–525 (2007).

    Google Scholar 

  31. Kas, M. J., de Mooij-van Malsen, A. J., Olivier, B., Spruijt, B. M. & Van Ree, J. M. Differential genetic regulation of motor activity and anxiety-related behaviors in mice using an automated home cage task. Behav. Neurosci. 122, 769–776 (2008).

    PubMed  Google Scholar 

  32. Thifault, S., Lalonde, R., Sanon, N. & Hamet, P. Longitudinal analysis of motor activity and coordination, anxiety, and spatial learning in mice with altered blood pressure. Brain Res. 910, 99–105 (2001).

    CAS  PubMed  Google Scholar 

  33. Brooks, S., Kaur, S., Starr, B. S. & Starr, M. S. Motor actions of eliprodil in the normal and monoamine-depleted mouse: a role in the treatment of Parkinson's disease? J. Neural Transm. 103, 737–748 (1996).

    CAS  PubMed  Google Scholar 

  34. Drai, D., Kafkafi, N., Benjamini, Y., Elmer, G. & Golani, I. Rats and mice share common ethologically relevant parameters of exploratory behavior. Behav. Brain Res. 125, 133–140 (2001).

    CAS  PubMed  Google Scholar 

  35. Hickey, M. A., Gallant, K., Gross, G. G., Levine, M. S. & Chesselet, M. F. Early behavioral deficits in R6/2 mice suitable for use in preclinical drug testing. Neurobiol. Dis. 20, 1–11 (2005).

    CAS  PubMed  Google Scholar 

  36. Valentinuzzi, V. S. et al. Locomotor response to an open field during C57BL/56J active and inactive phases: differences dependent on conditions of illumination. Physiol. Behav. 69, 269–275 (2000).

    CAS  PubMed  Google Scholar 

  37. Van Raamsdonk, J. M. et al. Phenotypic abnormalities in the YAC128 mouse model of Huntington disease are penetrant on multiple genetic backgrounds and modulated by strain. Neurobiol. Dis. 26, 189–200 (2007).

    CAS  PubMed  Google Scholar 

  38. Harri, M. et al. Effect of access to a running wheel on behavior of C57BL/56J mice. Lab. Anim. Sci. 49, 401–405 (1999).

    CAS  PubMed  Google Scholar 

  39. Kent, S., Hurd, M. & Satinoff, E. Interactions between body temperature and wheel running over the estrous cycle in rats. Physiol. Behav. 49, 1079–1084 (1991).

    CAS  PubMed  Google Scholar 

  40. Salam, J. N. et al. Voluntary exercise in C57 mice is anxiolytic across several measures of anxiety. Behav. Brain Res. 197, 31–40 (2008).

    PubMed  Google Scholar 

  41. Hastings, M. H., Maywood, E. S. & Reddy, A. B. Two decades of circadian time. J. Neuroendocrinol. 20, 812–819 (2008).

    CAS  PubMed  Google Scholar 

  42. Morton, A. J. et al. Disintegration of the sleep-wake cycle and circadian timing in Huntington's disease. J. Neurosci. 25, 157–163 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Dell'Omo, G. et al. Early behavioural changes in mice infected with BSE and scrapie: automated home cage monitoring reveals prion strain differences. Eur. J. Neurosci. 16, 735–742 (2002).

    PubMed  Google Scholar 

  44. Nielsen, D. M. et al. Paw preference, rotation, and dopamine function in Collins HI and LO mouse strains. Physiol. Behav. 61, 525–535 (1997).

    CAS  PubMed  Google Scholar 

  45. Nishimura, F. et al. Potential use of embryonic stem cells for the treatment of mouse parkinsonian models: improved behavior by transplantation of in vitro differentiated dopaminergic neurons from embryonic stem cells. Stem Cells 21, 171–180 (2003).

    PubMed  Google Scholar 

  46. Zhang, X., Andren, P. E., Greengard, P. & Svenningsson, P. Evidence for a role of the 5-HT1B receptor and its adaptor protein, p11, in L-DOPA treatment of an animal model of Parkinsonism. Proc. Natl Acad. Sci. USA 105, 2163–2168 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Ungerstedt, U. & Arbuthnott, G. W. Quantitative recording of rotational behaviour in rats after 6-hydroxydopamine lesions of the nigrostriatal dopamine system. Brain Res. 24, 485–493 (1970).

    CAS  PubMed  Google Scholar 

  48. Matsuya, T. et al. Synergistic effects of adenosine A2A antagonist and L-DOPA on rotational behaviors in 6-hydroxydopamine-induced hemi-Parkinsonian mouse model. J. Pharmacol. Sci. 103, 329–332 (2007).

    CAS  PubMed  Google Scholar 

  49. Yu, L., Schwarzschild, M. A. & Chen, J. F. Cross-sensitization between caffeine- and L-dopa-induced behaviors in hemiparkinsonian mice. Neurosci. Lett. 393, 31–35 (2006).

    CAS  PubMed  Google Scholar 

  50. Björklund, L. et al. Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc. Natl Acad. Sci. USA 99, 2344–2349 (2002).

    PubMed  PubMed Central  Google Scholar 

  51. Bensadoun, J. C., Mirochnitchenko, O., Inouye, M., Aebischer, P. & Zurn, A. D. Attenuation of 6-OHDA-induced neurotoxicity in glutathione peroxidase transgenic mice. Eur. J. Neurosci. 10, 3231–3236 (1998).

    CAS  PubMed  Google Scholar 

  52. Dunham, N. W. & Miya, T. S. A note on a simple apparatus for detecting neurological deficit in rats and mice. J. Am. Pharm. Assoc. 46, 208–209 (1957).

    CAS  Google Scholar 

  53. Jones, B. J. & Roberts, D. J. A rotarod suitable for quantitative measurements of motor inco-ordination in naive mice. Naunyn-Schmiedebergs Arch. Pharmacol. 259, 211 (1968).

    CAS  Google Scholar 

  54. Monville, C., Torres, E. M. & Dunnett, S. B. Comparison of two different protocols of the rotarod test to assess motor deficit and lesion size in the 6-OHDA model. J. Neurosci. Methods 158, 219–223 (2006). Although this study used rats, the findings are applicable to mouse models of disease. They demonstrate that different lesion types are differentially sensitive to different rotarod test protocols.

    PubMed  Google Scholar 

  55. Wallace, J. E., Krauter, E. E. & Campbell, B. A. Motor and reflexive behavior in the aging rat. J. Gerontol. 35, 364–270 (1980).

    CAS  PubMed  Google Scholar 

  56. Kiernan, B. W. et al. Myelination and behaviour of tenascin-C null transgenic mice. Eur. J. Neurosci. 11, 3082–3092 (1999).

    CAS  PubMed  Google Scholar 

  57. Perry, T. A. et al. Cognitive and motor function in transgenic mice carrying excess copies of the 695 and 751 amino acid isoforms of the amyloid precursor protein gene. Alz. Res. 1, 5–14 (1995).

    Google Scholar 

  58. Schallert, T., Woodlee, M. T. & Fleming, S. M. in Pharmacology of Cerebral Ischemia (eds Krieglstein, J. & Klumpp, S.) 201–216 (Medpharm Scientific Publishers, Stuttgart, 2002).

    Google Scholar 

  59. Heglund, N. C., Taylor, C. R. & McMahon, T. A. Scaling stride frequency and gait to animal size: mice to horses. Science 186, 1112–1113 (1974).

    CAS  PubMed  Google Scholar 

  60. Clarke, K. A. & Still, J. Development and consistency of gait in the mouse. Physiol. Behav. 73, 159–164 (2001). Demonstrates the use of video technology to measure several aspects of mouse gait in detail.

    CAS  PubMed  Google Scholar 

  61. Glynn, D., Drew, C. J., Reim, K., Brose, N. & Morton, A. J. Profound ataxia in complexin I knockout mice masks a complex phenotype that includes exploratory and habituation deficits. Hum. Mol. Genet. 14, 2369–2385 (2005).

    CAS  PubMed  Google Scholar 

  62. Guillot, T. S., Asress, S. A., Richardson, J. R., Glass, J. D. & Miller, G. W. Treadmill gait analysis does not detect motor deficits in animal models of Parkinson's disease or amyotrophic lateral sclerosis. J. Mot. Behav. 40, 568–577 (2008).

    PubMed  Google Scholar 

  63. Marshall, J. F., Richardson, J. S. & Teitelbaum, P. Nigrostriatal bundle damage and the lateral hypothalamic syndrome. J. Comp. Physiol. Psychol. 87, 808–830 (1974).

    CAS  PubMed  Google Scholar 

  64. Ogawa, N., Hirose, Y., Ohara, S., Ono, T. & Watanabe, Y. A simple quantitative bradykinesia test in MPTP-treated mice. Res. Commun. Chem. Pathol. Pharmacol. 50, 435–441 (1985).

    CAS  PubMed  Google Scholar 

  65. Ohno, Y. et al. Evaluation of the antibradykinetic actions of 5-HT1A agonists using the mouse pole test. Prog. Neuropsychopharmacol. Biol. Psychiatry 32, 1302–1307 (2008).

    CAS  PubMed  Google Scholar 

  66. Thullier, F., Lalonde, R., Cousin, X. & Lestienne, F. Neurobehavioral evaluation of lurcher mutant mice during ontogeny. Brain Res. Dev. Brain Res. 100, 22–28 (1997).

    CAS  PubMed  Google Scholar 

  67. Crawley, J. N. What's Wrong With My Mouse?: Behavioral Phenotyping of Transgenic and Knockout Mice (Wiley, New York, 2000). Probably the most informative text on behavioural phenotyping of the mouse.

    Google Scholar 

  68. Kashiwabuchi, N. et al. Impairment of motor coordination, Purkinje cell synapse formation, and cerebellar long-term depression in GluRδ2 mutant mice. Cell 81, 245–252 (1995).

    CAS  PubMed  Google Scholar 

  69. Lalonde, R., Qian, S. & Strazielle, C. Transgenic mice expressing the PS1-A246E mutation: effects on spatial learning, exploration, anxiety, and motor coordination. Behav. Brain Res. 138, 271–279 (2003).

    Google Scholar 

  70. Lalonde, R. & Strazielle, C. Motor coordination, exploration, and spatial learning in a natural mouse mutation (nervous) with Purkinje cell degeneration. Behav. Genet. 33, 59–66 (2003).

    CAS  PubMed  Google Scholar 

  71. Le Cudennec, C., Faure, A., Ly, M. & Delatour, B. One-year longitudinal evaluation of sensorimotor functions in APP751SL transgenic mice. Genes Brain Behav. 7 (Suppl. 1), 783–791 (2008).

    Google Scholar 

  72. Baskin, Y. K., Dietrich, W. D. & Green, E. J. Two effective behavioral tasks for evaluating sensorimotor dysfunction following traumatic brain injury in mice. J. Neurosci. Methods 129, 87–93 (2003).

    PubMed  Google Scholar 

  73. Farr, T. D., Liu, L., Colwell, K. L., Whishaw, I. Q. & Metz, G. A. Bilateral alteration in stepping pattern after unilateral motor cortex injury: a new test strategy for analysis of skilled limb movements in neurological mouse models. J. Neurosci. Methods 153, 104–113 (2006).

    PubMed  Google Scholar 

  74. Metz, G. A. & Whishaw, I. Q. Cortical and subcortical lesions impair skilled walking in the ladder rung walking test: a new task to evaluate fore- and hindlimb stepping, placing, and co-ordination. J. Neurosci. Methods 115, 169–179 (2002).

    PubMed  Google Scholar 

  75. Cabe, P. A., Tilson, H. A., Mitchell, C. L. & Dennis, R. A simple recording grip strength device. Pharmacol. Biochem. Behav. 8, 101–102 (1978).

    CAS  PubMed  Google Scholar 

  76. Joseph, J. A. & Lippa, A. S. Reduction of motor behavioral deficits in senescent animals via chronic prolactin administration. II. Non-stereotypic behaviors. Neurobiol. Aging 7, 37–40 (1986).

    CAS  PubMed  Google Scholar 

  77. van Riezen, H. & Boersma, L. A new method for quantitative grip strength evaluation. Eur. J. Pharmacol. 6, 353–356 (1969).

    CAS  PubMed  Google Scholar 

  78. Jodogne, C., Tirelli, E., Klingbiel, P. & Legros, J. J. Oxytocin attenuates tolerance not only to the hypothermic but also to the myorelaxant and akinesic effects of ethanol in mice. Pharmacol. Biochem. Behav. 40, 261–265 (1991).

    CAS  PubMed  Google Scholar 

  79. Lorivel, T. & Hilber, P. Motor effects of delta 9 THC in cerebellar Lurcher mutant mice. Behav. Brain Res. 181, 248–253 (2007).

    CAS  PubMed  Google Scholar 

  80. Whishaw, I. Q., Sarna, J. R. & Pellis, S. M. Evidence for rodent-common and species-typical limb and digit use in eating, derived from a comparative analysis of ten rodent species. Behav. Brain Res. 96, 79–91 (1998).

    CAS  PubMed  Google Scholar 

  81. Eshkol, N. & Wachmann, A. Movement Notation (Weidenfeld and Nicholson, London, 1958).

    Google Scholar 

  82. Whishaw, I. Q., Woodward, N. C., Miklyaeva, E. & Pellis, S. M. Analysis of limb use by control rats and unilateral DA-depleted rats in the Montoya staircase test: movements, impairments and compensatory strategies. Behav. Brain Res. 89, 167–177 (1997).

    CAS  PubMed  Google Scholar 

  83. Farr, T. D. & Whishaw, I. Q. Quantitative and qualitative impairments in skilled reaching in the mouse (Mus musculus) after a focal motor cortex stroke. Stroke 33, 1869–1875 (2002).

    PubMed  Google Scholar 

  84. Whishaw, I. Q. & Pellis, S. M. The structure of skilled forelimb reaching in the rat: a proximally driven movement with a single distal rotatory component. Behav. Brain Res. 41, 49–59 (1990).

    CAS  PubMed  Google Scholar 

  85. Whishaw, I. Q., Pellis, S. M., Gorny, B. P. & Pellis, V. C. The impairments in reaching and the movements of compensation in rats with motor cortex lesions: an endpoint, videorecording, and movement notation analysis. Behav. Brain Res. 42, 77–91 (1991).

    CAS  PubMed  Google Scholar 

  86. Whishaw, I. Q. An endpoint, descriptive, and kinematic comparison of skilled reaching in mice (Mus musculus) with rats (Rattus norvegicus). Behav. Brain Res. 78, 101–111 (1996).

    CAS  PubMed  Google Scholar 

  87. Whishaw, I. Q., O'Connor, W. T. & Dunnett, S. B. The contributions of motor cortex, nigrostriatal dopamine and caudate-putamen to skilled forelimb use in the rat. Brain 109, 805–843 (1986).

    PubMed  Google Scholar 

  88. Wells, J. E. et al. Matrix metalloproteinase (MMP)-12 expression has a negative impact on sensorimotor function following intracerebral haemorrhage in mice. Eur. J. Neurosci. 21, 187–196 (2005).

    PubMed  Google Scholar 

  89. Collins, R. L. On the inheritance of handedness. I. Laterality in inbred mice. J. Hered. 59, 9–12 (1968).

    CAS  PubMed  Google Scholar 

  90. Cabib, S. et al. Paw preference and brain dopamine asymmetries. Neuroscience 64, 427–432 (1995).

    CAS  PubMed  Google Scholar 

  91. Baird, A. L., Meldrum, A. & Dunnett, S. B. The staircase test of skilled reaching in mice. Brain Res. Bull. 54, 243–250 (2001). Demonstration of the staircase test in mice as a method to assess fine motor control.

    CAS  PubMed  Google Scholar 

  92. Puskovic, V. et al. Prolonged biologically active transgene expression driven by HSV LAP2 in brain in vivo. Mol. Ther. 10, 67–75 (2004).

    CAS  PubMed  Google Scholar 

  93. Starkey, M. L. et al. Assessing behavioural function following a pyramidotomy lesion of the corticospinal tract in adult mice. Exp. Neurol. 195, 524–539 (2005).

    PubMed  Google Scholar 

  94. Bouet, V. et al. Sensorimotor and cognitive deficits after transient middle cerebral artery occlusion in the mouse. Exp. Neurol. 203, 555–567 (2007).

    PubMed  Google Scholar 

  95. Paylor, R. & Crawley, J. N. Inbred strain differences in prepulse inhibition of the mouse startle response. Psychopharmacology (Berl.) 132, 169–180 (1997). This paper shows the sensitivity of prepulse inhibition across a range of inbred mouse strains.

    CAS  Google Scholar 

  96. Hoffman, H. S. & Searle, J. L. Acoustic variables in the modification of startle reaction in the rat. J. Comp. Physiol. Psychol. 60, 53–58 (1965).

    CAS  PubMed  Google Scholar 

  97. Grillon, C., Ameli, R., Charney, D. S., Krystal, J. & Braff, D. Startle gating deficits occur across prepulse intensities in schizophrenic patients. Biol. Psychiatry 32, 939–943 (1992).

    CAS  PubMed  Google Scholar 

  98. Perriol, M. P. et al. Disturbance of sensory filtering in dementia with Lewy bodies: comparison with Parkinson's disease dementia and Alzheimer's disease. J. Neurol. Neurosurg. Psychiatry 76, 106–108 (2005).

    PubMed  PubMed Central  Google Scholar 

  99. Swerdlow, N. R. et al. Impaired prepulse inhibition of acoustic and tactile startle response in patients with Huntington's disease. J. Neurol. Neurosurg. Psychiatry 58, 192–200 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Semenova, S., Geyer, M. A., Sutcliffe, J. G., Markou, A. & Hedlund, P. B. Inactivation of the 5-HT7 receptor partially blocks phencyclidine-induced disruption of prepulse inhibition. Biol. Psychiatry 63, 98–105 (2008).

    CAS  PubMed  Google Scholar 

  101. Yee, B. K., Chang, D. L. & Feldon, J. The effects of dizocilpine and phencyclidine on prepulse inhibition of the acoustic startle reflex and on prepulse-elicited reactivity in C57BL6 mice. Neuropsychopharmacology 29, 1865–1877 (2004).

    CAS  PubMed  Google Scholar 

  102. Van Raamsdonk, J. M. et al. Cognitive dysfunction precedes neuropathology and motor abnormalities in the YAC128 mouse model of Huntington's disease. J. Neurosci. 25, 4169–4180 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Plappert, C. F., Rodenbucher, A. M. & Pilz, P. K. Effects of sex and estrous cycle on modulation of the acoustic startle response in mice. Physiol. Behav. 84, 585–594 (2005).

    CAS  PubMed  Google Scholar 

  104. Willott, J. F. et al. The BALB/c mouse as an animal model for progressive sensorineural hearing loss. Hear. Res. 115, 162–174 (1998).

    CAS  PubMed  Google Scholar 

  105. Mackintosh, N. J. The Psychology of Animal Learning (Academic, 1974).

    Google Scholar 

  106. Humby, T., Laird, F. M., Davis, W. & Wilkinson, L. S. Visuospatial attentional functioning in mice: interactions between cholinergic manipulations and genotype. Eur. J. Neurosci. 11, 2813–2823 (1999). Demonstration of the five-choice reaction time task for operant motor learning in the mouse in the nine-hole box.

    CAS  PubMed  Google Scholar 

  107. Baron, S. P. & Meltzer, L. T. Mouse strains differ under a simple schedule of operant learning. Behav. Brain Res. 118, 143–152 (2001).

    CAS  PubMed  Google Scholar 

  108. Bensadoun, J. C., Brooks, S. P. & Dunnett, S. B. Free operant and discrete trial performance of mice in the 9-hole box apparatus: validation using amphetamine and scopolamine. Psychopharmacology (Berl.) 174, 396–405 (2004).

    CAS  Google Scholar 

  109. Derenne, A., Arsenault, M. L., Austin, D. P. & Weatherly, J. N. Weaver mutant mice exhibit long-term learning deficits under several measures of instrumental behavior. Physiol. Behav. 92, 1002–1009 (2007).

    CAS  PubMed  Google Scholar 

  110. Carli, M., Robbins, T. W., Evenden, J. L. & Everitt, B. J. Effects of lesions to ascending noradrenergic neurones on performance of a 5-choice serial reaction task in rats; implications for theories of dorsal noradrenergic bundle function based on selective attention and arousal. Behav. Brain Res. 9, 361–380 (1983).

    CAS  PubMed  Google Scholar 

  111. Cho, Y. H., Delcasso, S., Israel, A. & Jeantet, Y. A long list visuo-spatial sequential learning in mice. Behav. Brain Res. 179, 152–158 (2007).

    PubMed  Google Scholar 

  112. Christie, M. A. & Hersch, S. M. Demonstration of nondeclarative sequence learning in mice: development of an animal analog of the human serial reaction time task. Learn. Mem. 11, 720–723 (2004).

    PubMed  Google Scholar 

  113. Trueman, R. C., Brooks, S. P. & Dunnett, S. B. Implicit learning in a serial choice visual discrimination task in the operant 9-hole box by intact and striatal lesioned mice. Behav. Brain Res. 159, 313–322 (2005).

    PubMed  Google Scholar 

  114. Brooks, S. P., Trueman, R. C. & Dunnett, S. B. Striatal lesions in the mouse disrupt acquisition and retention, but not implicit learning, in the SILT procedural motor learning task. Brain Res. 1185, 179–188 (2007).

    CAS  PubMed  Google Scholar 

  115. Trueman, R. C., Brooks, S. P., Jones, L. & Dunnett, S. B. Time course of choice reaction time deficits in the HdhQ92/Q92 knock-in mouse model of Huntington's disease in the operant Serial Implicit Learning Task (SILT). Behav. Brain Res. 189, 317–324 (2008). This paper demonstrates the sensitivity of the SILT to motor learning in a knock-in mouse model of disease.

    PubMed  Google Scholar 

  116. Wrenn, C. C. et al. Performance of galanin transgenic mice in the 5-choice serial reaction time attentional task. Pharmacol. Biochem. Behav. 83, 428–440 (2006).

    CAS  PubMed  Google Scholar 

  117. Marsden, C. D. & Parkes, J. D. Success and problems of long-term levodopa therapy in Parkinson's disease. Lancet 1, 345–349 (1977).

    CAS  PubMed  Google Scholar 

  118. Ohl, F. Animal models of anxiety. Handb. Exp. Pharmacol. 169, 35–69 (2005).

    Google Scholar 

  119. Caligiuri, M. P. & Buitenhuys, C. Do preclinical findings of methamphetamine-induced motor abnormalities translate to an observable clinical phenotype? Neuropsychopharmacology 30, 2125–2134 (2005).

    CAS  PubMed  Google Scholar 

  120. Willner, P. The validity of animal models of depression. Psychopharmacology (Berl.) 83, 1–16 (1984).

    CAS  Google Scholar 

  121. Lalonde, R. & Strazielle, C. Brain regions and genes affecting postural control. Prog. Neurobiol. 81, 45–60 (2007).

    CAS  PubMed  Google Scholar 

  122. Winer, B. J., Brown, D. R. & Michels, K. M. Statistical Principles in Experimental Design (McGraw-Hill, New York, 1991).

    Google Scholar 

  123. Robinson, V. Finding alternatives: an overview of the 3Rs and the use of animals in research. Sch. Sci. Rev. 87, 111–114 (2005).

    Google Scholar 

  124. Masuya, H. et al. Implementation of the modified-SHIRPA protocol for screening of dominant phenotypes in a large-scale ENU mutagenesis program. Mamm. Genome 16, 829–837 (2005).

    PubMed  Google Scholar 

  125. Inoue, M. et al. Sensory stimulation accelerates dopamine release in the basal ganglia. Brain Res. 1026, 179–184 (2004).

    CAS  PubMed  Google Scholar 

  126. Ferdinandusse, S. et al. Ataxia with loss of Purkinje cells in a mouse model for Refsum disease. Proc. Natl Acad. Sci. USA 105, 17712–17717 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Lackner, P. et al. Behavioural and histopathological alterations in mice with cerebral malaria. Neuropathol. Appl. Neurobiol. 32, 177–188 (2006).

    CAS  PubMed  Google Scholar 

  128. Lalonde, R., Dumont, M., Paly, E., London, J. & Strazielle, C. Characterization of hemizygous SOD1/wild-type transgenic mice with the SHIRPA primary screen and tests of sensorimotor function and anxiety. Brain Res. Bull. 64, 251–258 (2004).

    CAS  PubMed  Google Scholar 

  129. Rafael, J. A., Nitta, Y., Peters, J. & Davies, K. E. Testing of SHIRPA, a mouse phenotypic assessment protocol, on Dmd(mdx) and Dmd(mdx3cv) dystrophin-deficient mice. Mamm. Genome 11, 725–728 (2000).

    CAS  PubMed  Google Scholar 

  130. Harms, L. R., Eyles, D. W., McGrath, J. J., Mackay-Sim, A. & Burne, T. H. Developmental vitamin D deficiency alters adult behaviour in 129/SvJ and C57BL/56J mice. Behav. Brain Res. 187, 343–350 (2008).

    CAS  PubMed  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. The Brain Repair Group, School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AX, South Wales, UK

    Simon P. Brooks & Stephen B. Dunnett

  2. Simon P. Brooks & Stephen B. Dunnett

Authors
  1. Simon P. Brooks
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stephen B. Dunnett
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

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.

Supplementary information

Supplementary information S1

Supplementary information S1 movie (WMV 6654 kb)

Supplementary information S2

Supplementary information S2 movie (WMV 4669 kb)

Supplementary information S3

Supplementary information S3 movie (WMV 3638 kb)

Supplementary information S4

Supplementary information S4 movie (WMV 2107 kb)

Supplementary information S5

Supplementary information S5 movie (WMV 2396 kb)

Supplementary information S6

Supplementary information S6 movie (WMV 2794 kb)

Supplementary information S7

Supplementary information S7 movie (WMV 2677 kb)

Supplementary information S8

Supplementary information S8 movie (WMV 3789 kb)

Supplementary information S9

Supplementary information S9 movie (WMV 3029 kb)

Supplementary information S10

Supplementary information S10 movie (WMV 3521 kb)

Related links

Related links

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.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrn2652

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing