The pharmacological sensitivity of a touchscreen-based visual discrimination task in the rat using simple and perceptually challenging stimuli.

RATIONALE: Cognitive testing with touchscreen-equipped operant boxes ('touchscreens') is becoming increasingly popular. Tasks, such as paired associate learning or reversal learning of visual stimuli, have the discrimination of visual stimuli as a fundamental component. However, the effect of drugs commonly used in the study of cognitive mechanisms has yet to be described in a visual discrimination. OBJECTIVE: The objective of the study was to profile a range of psychoactive agents (glutamatergic, dopaminergic, and cholinergic agonists and antagonists) known to be important in cognitive processing on visual discrimination performance using a touch sensitive computer monitor. METHODS: Male Lister Hooded rats were trained to a stable level of performance in a simple visual discrimination. In Experiment 1, the effect of MK-801, phencyclidine, memantine, dextroamphetamine sulphate (D-amphetamine) and scopolamine was assessed. In Experiment 2, the stimuli were blended together resulting in a perceptually more demanding discrimination and a reduction in accuracy. The rats used in Experiment 1 were then retested with these 'morphed' stimuli under the influence of the above compounds. RESULTS: MK-801, PCP, and D-amphetamine induced selective deficits in accuracy in both versions of the task. In contrast, scopolamine and memantine produced non-selective deficits in accuracy. Morphing the stimuli reduced accuracy, but did not alter the observed behavioural profile after compound administration. CONCLUSION: These data improve our understanding of the basic neuropharmacology of a visual discrimination in cognitive tests employing touchscreens and will aid in the interpretation of pharmacological studies with more cognitively demanding methodologies.

Trial-unique, delayed nonmatching-to-location (TUNL): a novel, highly hippocampus-dependent automated touchscreen test of location memory and pattern separation.

The hippocampus is known to be important for learning and memory, and is implicated in many neurodegenerative diseases. Accordingly many animal models of learning and memory focus on hippocampus-dependent tests of location learning and memory. These tests often use dry mazes or water mazes; however automated testing in operant chambers confers many advantages over such methods. Some automated tests of location memory, such as delayed nonmatching-to-position (DNMTP) have, however, fallen out of favor following the discovery that such tasks can be solved using mediating behaviors that can bridge the delay and reduce the requirement for memory per se. Furthermore some researchers report that DNMTP performance may not always require the hippocampus. Thus, in an attempt to develop a highly hippocampus-dependent automated test of location memory that elicits fewer mediating behaviors, we have developed a trial-unique nonmatching-to-location (TUNL) task, carried out in a computer-automated touchscreen testing apparatus. To test the efficacy of this assay, rats with lesions to the hippocampus, or a sham lesion control group, were tested under a variety of conditions. Both groups were able to perform well at a delay of 1s, but the lesion group was highly impaired when tested at a 6s delay. Moreover, animals with lesions of the hippocampus showed a greater impairment when the distance between the locations was reduced. This result indicates that TUNL can be used to investigate both memory across a delay, and spatial pattern separation (the ability to disambiguate similar spatial locations). Performance-enhancing mediating behaviors during the task were found to be minimal. Thus, the TUNL task has the potential to serve as a powerful tool for the study of the neurobiology of learning and memory.

A novel touchscreen-automated paired-associate learning (PAL) task sensitive to pharmacological manipulation of the hippocampus: a translational rodent model of cognitive impairments in neurodegenerative disease.

RATIONALE: Paired-associate learning (PAL), as part of the Cambridge Neuropsychological Test Automated Battery, is able to predict who from an at-risk population will develop Alzheimer's disease. Schizophrenic patients are also impaired on this same task. An automated rodent model of PAL would be extremely beneficial in further research into Alzheimer's disease and schizophrenia. OBJECTIVE: The objective of this study was to develop a PAL task using touchscreen-equipped operant boxes and test its sensitivity to manipulations of the hippocampus, a brain region of interest in both Alzheimer's disease and schizophrenia. MATERIALS AND METHODS: Previous work has shown that spatial and non-spatial memory can be tested in touchscreen-equipped operant boxes. Using this same apparatus, rats were trained on two variants of a PAL task differing only in the nature of the S- (the unrewarded stimuli, a combination of image and location upon the screen). Rats underwent cannulation of the dorsal hippocampus, and after recovery were tested under the influence of intra-hippocampally administered glutamatergic and cholinergic antagonists while performing the PAL task. RESULTS: Impairments were seen after the administration of glutamatergic antagonists, but not cholinergic antagonists, in one of the two versions of PAL. CONCLUSIONS: De-activation of the hippocampus caused impairments in a PAL task. The selective nature of this effect (only one of the two tasks was impaired), suggests the effect is specific to cognition and cannot be attributed to gross impairments (changes in visual learning). The pattern of results suggests that rodent PAL may be suitable as a translational model of PAL in humans.

Hippocampal lesions in rats impair learning and memory for locations on a touch-sensitive computer screen: the "ASAT" task.

It has been repeatedly demonstrated across species that the hippocampus is critical for spatial learning and memory. Consequently, numerous paradigms have been created to study spatial learning in the rodent. Most of these tasks, such as the Morris water maze, 8-arm radial maze, and T-maze, are non-automated procedures. It was our goal to create an automated task in the rodent that is quickly learned, hippocampal-dependent, and minimizes the confounding variables present in most tests measuring hippocampal-dependent learning and memory. To accomplish this, we created a novel search task using a standard operant box fitted with a touch-sensitive computer monitor. Subjects were required to locate an S+ "hidden" amongst other identical stimuli on the monitor. In two versions of the task the S+ stayed in the same location within a session but shifted location between sessions. In a third version of the task the S+ was moved to a new location after every 10 trials. It was found that the location of the S+ was quickly acquired each day (within 10 trials), and that the hippocampal-lesion group was impaired when compared to their control cohort. With the benefits inherent in automation, these tasks confer significant advantages over traditional tasks used to study spatial learning and memory in the rodent. When combined with previously developed non-spatial cognitive tests that can also be run in the touch-screen apparatus, the result is a powerful cognitive test battery for the rodent.