Examining Cognitive Performance in Mice using the Open-Source Operant Feeding Device FED3

Cognitive impairments are prevalent in various neurological disorders, including chronic pain conditions, and pose significant therapeutic challenges. Preclinical rodent models serve as valuable tools for investigating the underlying mechanisms of and treatments for cognitive dysfunction. However, factors such as stress, age, sex, and disease duration present challenges to reliably capturing cognitive deficits in rodents. Here, we present a comprehensive and high-throughput protocol utilizing the open-source operant Feeding Experimentation Device 3 (FED3) for assessing cognitive performance in mice. We developed a data pipeline to streamline data compilation and analysis, and established operating conditions for a six-test cognitive battery which can be completed in as few as 20 days. We validated our testing procedures using bilateral orbitofrontal cortical lesions to capture deficits in executive function, and demonstrated the feasibility of assessing cognitive function in aged mice of both sexes to identify genotypic and sex-specific effects. Overall, our findings demonstrate that the FED3 is a versatile tool for evaluating cognitive function in mice, offering a low-cost, high-throughput approach for preclinical studies of neurological disorders. We anticipate that this protocol will facilitate broader implementation of cognitive testing in rodent models and contribute to the understanding and treatment of cognitive dysfunction in neurological diseases.