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

Abstract

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. 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. 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. Impairments were seen after the administration of glutamatergic antagonists, but not cholinergic antagonists, in one of the two versions of PAL. 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.