Insights into Age-Related Cognitive Decline: Coupling Neurophysiological and Behavioral Approaches

Abstract

A major goal of research in systems and behavioral neuroscience today is to understand how our brains produce the complex and diverse behaviors that reflect what we refer to as cognition. Tremendous gains have been made over the past century in understanding the neural bases of behavior. These include insights into the basic cellular mechanisms of information processing and storage, and the identification of brain circuits critical to specific behaviors. Some studies have focused on how such neuronal networks develop in early life, reach full functional maturity, and change during aging. Defining the factors that determine successful versus pathological cognitive aging is a particularly important goal because, in most developed countries, the fastest growing segment of the population is those over 85 years of age. Although there has been significant improvement in the precision of the cognitive test batteries developed for humans across the life span, as well as improvements in the resolution and specificity of brain imaging methods, animal models of cognitive aging continue to play a critical role in revealing the brain mechanisms responsible for normal behavioral function. The use of such animal models is most productive when the cognitive operations studied depend on brain structures whose function is conserved across evolution. The circular platform spatial memory task (“Barnes Maze”) was developed to be sensitive to the function of specific brain circuits within the temporal lobe hypothesized to be important for memory in both humans and rodents, and likely to change with age. This chapter provides a personal account of the development of the circular platform task and a historical perspective regarding the overall goal for the design to develop an effective task for aged animals that minimizes task demand stress and ensures sensitivity to even small changes in the cognitive domain investigated. Detailed discussion in this chapter includes how past and newer research have converged, and have uncovered relations between memory and place cell functioning in the hippocampus by coupling neurophysiological and behavioral methodologies. This approach has allowed great insight into the processes underlying learning and memory, and has been particularly fruitful in elucidating the underpinnings of age-related cognitive decline.