“All putative animal models [of neuropsychiatric disorders] should be evaluated with the broadest range possible of behavioral assays” – Nestler & Hyman 2010
Although each of the above tasks can be used alone, we would advocate the use of a ‘battery’ approach to establish a cognitive profile of an animal. In this way a given task in the battery not only yields useful results in its own right, it can serve as a control for other tasks in the battery. Thus, if an animal fails object-place paired associate learning but performs well on visual discrimination and reversal, it is unlikely that the paired associate learning impairment is due to a difficulty with perceptually discriminating objects. Similarly if an animal is impaired on TUNL but not 5-CSRTT, an attentional explanation for the TUNL impairment would seem unlikely. These comparisons can be made with confidence, because all of the tasks use the same types of stimuli, responses and reward, and of course are all carried out in the same testing apparatus.
Yet to suggest a battery approach is not to suggest slavish adherence to animmutable sequence of tests; for example each of these tasks can be followed by behavioural probes to follow up interesting findings. For example, shape or photographic stimuli can be ‘morphed’ to increase the premium on perceptual discrimination (McCarthy et al, 2011
). Parameters in TUNL can be further varied, for example inter-trial intervals might be varied to increase or decrease interference. The 5-CSRTT can be followed by sessions of rapid presentation of stimuli during long sessions in order to examine sustained vigilance. And so on.
How, practically, does one implement the battery? There are different models, depending on one’s needs. The extremes are 1. Run each task in a new cohort of naïve animals, or 2. Run many tasks in each animal (we are currently working out what tasks ‘go together’ best, and are settling on a sequence in which the tasks appear not to interfere with one another). Option 1 might be the better choice for, say, a progressive disease model or a drug study; option 2 has its own advantages, for example fewer animals are used, which is desirable in cases where large numbers of animals are difficult to obtain. Which approach is taken depends on several factors that may differ from experiment to experiment.
Finally of course brand new tasks for the battery are being developed all the time, some of which could prove particularly useful for schizophrenia research; we have already alluded above to attentional set-shifting tests similar to those administered using the CANTAB method (Leeson et al., 2009b
); in addition we are having success developing a touchscreen version of the object recognition memory test used so widely to study animal models of schizophrenia(e.g., Duffy et al.; Grayson et al., 2007
). Furthermore, some researchers are currently expanding the method to incorporate other techniques such as in vivo
electrophysiology and dialysis.
Are there any disadvantages to this method? An obvious one is that, being a relatively new method, there does not yet exist the extensive database behind it that some methods – for example, the Morris water maze – enjoy. But the touchscreen database is expanding: at this time we know of roughly 30 labs using touchscreen technology with rodents, and so the validation and development of this method is continuing apace. Another has been alluded to above: although the touchscreen method avoids the aversive stimuli and stressors endemic to some other methods, any method which uses gustatory rewards is vulnerable to the potential effects of some perturbations on motivation to perform for reward. Indeed we have experienced such problems with certain mouse models, and to some extent were able to mitigate them by, for example, using larger volumes of highly palatable reinforcers (e.g., 20ul strawberry milkshake), and requiring fewer trials per session (from the control groups as well, of course). Finally, although all things considered we strongly advocate a battery approach in which all tests are carried out in the same apparatus, such an approach might make within-subjects task designs more vulnerable to negative or positive transfer between tasks. Of course this is a potential problem when any within-subjects battery is used; however the problem could be exacerbated when contexts are so similar between tasks. When designing within-subjects testing sequences, we try to combine tests which are least likely to interfere with one another – although such interference can only be definitively ruled out by retesting naive animals on the task in question.
There is still much work to be done. Much more validation is required to establish the neural circuits and transmitters involved in the tasks. We are currently piloting the mouse and rat tasks in human subjects, to allow even tighter translation and the ability to test whether the same circuits, neurotransmitters etc, and psychological processes (e.g., habit versus goal-directed performance) are involved in these tasks in rodents and humans. Another issue we will need to address is test-retest reliability, and what are the pharmacological sensitivities of each of the tasks. What is already clear from the foregoing discussion is that the touchscreen method offers much more than a ‘glorified Skinner box’. The apparatus can theoretically be used to run any task that can be run in a box with lights and levers, but the myriad of stimuli that are possible, and the multiple locations in which they can be presented, offer virtually unlimited possibilities for task development.