Validation of an Innovative Touchscreen System to Assess Neurocognitive Functions in Rodents

Neurodegenerative diseases such as Parkinson’s and Alzheimer’s are characterized by progressive cognitive deterioration, against which there exist currently only symptomatic therapies. Plant secondary metabolites with neuroprotective, anti-inflammatory, and antioxidant efficacies have attracted much research in recent years as future cognitive promoters. It is not yet certain, however, that there is a direct relationship between such activity and cognitive enhancement in healthy subjects. It was the aim of the current thesis to construct and validate a translational behavioral platform for testing cognitive functions in healthy (naive) C57BL/6J mice, against which future research regarding the cognitive and neurochemical effects of selected plant extracts might be benchmarked. The study developed and tested touchscreen behavioral testing with six unique tasks to measure multiple cognitive functions. We employed Pairwise Visual Discrimination (PVD) and Paired Associate Learning (PAL), primarily cholinergically mediated; attention and inhibitory control paradigms, including the 5-Choice Serial Reaction Time Task (5-CSRTT) and the Rodent Continuous Performance Test (rCPT), based on dopaminergic and noradrenergic transmissions; Trial-Unique Nonmatching-to-Location (TUNL), corresponding with glutamatergic functioning; and the 4-Choice Gambling Task (4-CGT), based on dopaminergic systems. This neurochemically informed design also allows future potential for combining behavioral and molecular data. Baseline performance demonstrated successful task acquisition and stable performance between sessions. PVD performance reached roughly 80% correct after session 20 and PAL performance improved from 50% to 80% over 55 sessions. In attention paradigms, shorter stimulus duration led to decreased accuracy and increased omissions. TUNL performance was significantly impaired at minimal spatial separation. Also, rCPT results showed increased hit rates and decreased false alarms across stages. In the 4-CGT task, mice demonstrated stable performance but did not display a clear preference for good options on free-choice trials. This translationally informative and reproducible behavioral system provides an empirically corroborated system of preclinical cognitive testing in our laboratory. As well as, due to limited data availability at the time of writing this thesis, only preliminary information related to the animal control section was accessible; therefore, the plant-based component could not be included in the present study. Nevertheless, this work paves the way for future research on the effects of plant-derived compounds on neurochemistry and cognition, with a second phase planned to investigate the efficacy and underlying mechanisms of selected extracts in modulating cognitive functions.