Measuring cognitive deficits in disabled mice using an automated interactive touchscreen system

Morton, A. Jennifer; Skillings, Elizabeth A.; Bussey, Timothy J.; Saksida, Lisa M.

doi:10.1038/nmeth1006-767

Cited by 82 publications

(68 citation statements)

References 5 publications

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“…To study the effect of exercise on dentate gyrus-mediated pattern separation, adult and aged mice were tested on a spatial discrimination task (29) carried out in an automated touch-screen testing system (27,30). Running selectively enhanced spatial touch-screen performance when stimuli were presented in close proximity in adult mice.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, previous studies may have been confounded by possible changes in motor skills. In the present study, a touch-screen method was used, which has minimal motor requirements (27,30).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, ablation of adult neurogenesis by x-irradiation or injection of lentivirus expressing dominant-negative Wnt (25,26) impaired performance in the radial arm maze only when the rewarded arm was in close proximity to the sample arm (20). In addition, in a nonnavigational touch-screen system (27), irradiated mice could not distinguish between small differences (20). Although these are important observations, the potential effects of increased neurogenesis on pattern separation have not been researched.…”

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Running enhances spatial pattern separation in mice

Creer

Romberg

Saksida

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

461

464

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Increasing evidence suggests that regular exercise improves brain health and promotes synaptic plasticity and hippocampal neurogenesis. Exercise improves learning, but specific mechanisms of information processing influenced by physical activity are unknown. Here, we report that voluntary running enhanced the ability of adult (3 months old) male C57BL/6 mice to discriminate between the locations of two adjacent identical stimuli. Improved spatial pattern separation in adult runners was tightly correlated with increased neurogenesis. In contrast, very aged (22 months old) mice had impaired spatial discrimination and low basal cell genesis that was refractory to running. These findings suggest that the addition of newly born neurons may bolster dentate gyrus-mediated encoding of fine spatial distinctions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Running enhances spatial pattern separation in mice

Creer

Romberg

Saksida

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

461

464

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“…1A) developed the touchscreen testing method for rats, a method which has more recently been adapted for mice (Izquierdo et al 1993;Bussey et al 2001b;Brigman et al 2005;Morton et al 2006). This computer-automated behavioral testing method allows computer graphic stimuli to be presented to a rodent and the rodent to respond to the computer screen via a nose-poke directly to the stimulus.…”

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confidence: 99%

“…In addition to the advantages of facilitated translation between human and animal tests, the task offers many other advantages, including low motoric demand, ease of administration, and accuracy of task parameters. The method has been used effectively in a number of behavioral, lesion, and pharmacological studies (e.g., Izquierdo et al 1993;Sahgal and Steckler 1994;Steckler and Sahgal 1995;Markham et al 1996;Bussey et al 1997aBussey et al ,b, 1998Bussey et al , 2001aParkinson et al 1999Parkinson et al , 2002Chudasama et al 2001;Chudasama and Robbins 2003;Cook et al 2004;Dalley et al 2005;Janisewicz and Baxter 2003;Brigman et al 2005;Minini and Jeffery 2006;Morton et al 2006).…”

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confidence: 99%

The touchscreen cognitive testing method for rodents: How to get the best out of your rat

Bussey¹,

Padain²,

Skillings³

et al. 2008

Learn. Mem.

235

222

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The touchscreen testing method for rodents is a computer-automated behavioral testing method that allows computer graphic stimuli to be presented to rodents and the rodents to respond to the computer screen via a nose-poke directly to the stimulus. The advantages of this method are numerous; however, a systematic study of the parameters that affect learning has not yet been conducted. We therefore sought to optimize stimuli and task parameters in this method. We found that when parameters were optimized, Lister Hooded rats could learn rapidly using this method, solving a discrimination of two-dimensional stimuli to a level of 80% within five to six sessions lasting ∼30 min each.In a final experiment we tested both male and female rats of the albino Sprague-Dawley strain, which are often assumed to have visual abilities far too poor to be useful for studies of visual cognition. The performance of female Sprague-Dawley rats was indistinguishable from that of their male counterparts. Furthermore, performance of male Sprague-Dawley rats was indistinguishable from that of their Lister Hooded counterparts. Finally, Experiment 5 examined the ability of Lister Hooded rats to learn a discrimination between photographic stimuli. Under conditions in which parameters were optimized, rats were remarkably adept at this discrimination. Taken together, these experiments served to optimize the touchscreen method and have demonstrated its usefulness as a high-throughput method for the cognitive testing of rodents.It is now well understood that the use of animal models is an essential component in our quest to understand the brain mechanisms of cognition. In addition, such models are necessary for researchers to be able to test potential therapeutic agents in a direct and expedient manner that is not possible in human subjects. Moreover, we are experiencing a revolution in the sophistication of transgenic and knock-out animal models that creates opportunities for cognitive testing and therapeutic screening that were until recently, unthinkable (Kobayashi and Chen 2005).To achieve successful translation of findings from animal models to humans, the cognitive tasks we use with our rodents should resemble as closely as possible those used with human subjects. Increasingly, human subjects are tested using computerautomated methods. A particularly powerful approach is the "touchscreen" testing method, in which subjects respond directly to stimuli on a computer screen (e.g., Robbins et al. 1994). The advantages of this method are numerous and include facilitated performance due to contiguity between stimuli and responses and the ability to present a battery of different cognitive tests in which parameters such as stimuli, responses, and feedback are consistent across tasks and conditions.To create a cognitive testing method for rodents that matched, as far as possible, the touchscreen testing method for humans, Bussey et al. (1994Bussey et al. ( , 1997a) (see Fig. 1A) developed the touchscreen testing method for rats, a method which has...

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Beneficial effects of environmental enrichment and food entrainment in the R6/2 mouse model of Huntington's disease

2014

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BackgroundIn addition to their cognitive and motor deficits, R6/2 mice show a progressive disintegration in circadian rhythms that mirrors the problems associated with sleep-wake disturbances experienced by patients with Huntington's disease (HD). It has been shown previously that motor and cognitive performance, as well as survival, can be improved in transgenic mouse models of HD through the provision of environmental enrichment.MethodsWe compared the effect of two different overnight entrainment paradigms presented either separately or in combination. The first was environmental enrichment, the second was temporal food-entrainment. Environmental enrichment was provided in the dark period (the natural active period for mice) in the form of access to a Perspex playground containing running wheels, tunnels, climbing frame, ropes and chew blocks. Food entrainment was imposed by allowing access to food only during the dark period. We assessed a number of different aspects of function in the mice, measuring general health (by SHIRPA testing, body temperature and body weight measurements), cognitive performance in the touchscreen and locomotor behavior in the open field.ResultsThere were no significant differences in cognitive performance between groups on different schedules. Environmental enrichment delayed the onset of general health deterioration, while food entrainment slowed the loss of body weight, aided the maintenance of body temperature and improved locomotor behavior. Effects were limited however, and in combination had deleterious effects on survival.ConclusionsOur results support previous studies showing that environmental enrichment can be beneficial and might be used to enhance the quality of life of HD patients. However, improvements are selective and ‘enrichment’ per se is likely to only be useful as an adjunct to a more direct therapy.

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Measuring cognitive deficits in disabled mice using an automated interactive touchscreen system

Cited by 82 publications

References 5 publications

Running enhances spatial pattern separation in mice

Running enhances spatial pattern separation in mice

The touchscreen cognitive testing method for rodents: How to get the best out of your rat

Beneficial effects of environmental enrichment and food entrainment in the R6/2 mouse model of Huntington's disease

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