Role of Prefrontal-Hippocampal Interactions in Age-Related Deficits in Spatial Working Memory

Abstract

The aging population is particularly susceptible to cognitive deficits, and as aging progresses, deficits in learning and memory can be observed. The hippocampus (HC) and prefrontal cortex (PFC) are vital regions in decision-making and spatial memory tasks. However, changes in aging are not uniform across these brain structures. Deteriorations in HC-PFC synchrony can lead to alterations in memory encoding, storage, and retrieval, ultimately resulting in age-related deficits in cognitive performance. The medial prefrontal cortex (mPFC) supports working memory, while the HC supports the acquisition of new episodic memories, including spatial memory. Studying age-related changes in these regions, and interactions between these regions, could give us valuable insight into the underlying mechanism of these age-related deficits. To investigate the functional differences of the mPFC and HC with age, healthy young (8 months) and aged (22 months) F344 rats were tested on a multi-stage cognitive behavioral battery of tasks that assess integrated and independent HC and mPFC function. On the Morris watermaze, subjects underwent spatial navigation trials (spatial memory), visual trials, and working memory trials. They were then tested on the temporal order memory task (working memory). The final task is a spatial alternation task rendered with an inbound component (spatial memory) and an outbound component (spatial memory and working memory). An implanted dual-bundle hyperdrive simultaneously records electrophysiological signals from the CA1 regions of the ventral HC and infralimbic and prelimbic regions of mPFC during the spatial alternation task. When comparing the performance of aged and young rats, aged rats were more impaired in the spatial navigation and working memory tasks on the Morris Watermaze, the Temporal Order Memory task, and the outbound component of the spatial alternation task. These results indicate impairments in the PFC and hippocampal regions, as well as interactions between them.