The Impact of mPFC-vHC Oscillatory Synchrony on Age-Related Deficits in Spatial Working Memory

Abstract

Among the cognitive functions susceptible to age-related decline, spatial and working memory functions are particularly affected. The hippocampus (HC) and medal prefrontal cortex (mPFC) are two brain regions essential for executing these cognitive processes. Communication between these regions is thought to be facilitated by theta (6-12Hz) oscillations, and increased theta synchrony between these regions is has been shown to correlate with improved performance on spatial working memory tasks. However, the impact of aging on interactions between these regions and their relationship to declines in spatial working memory function is unclear. To investigate these differences, we trained healthy young (9 months) and aged (22 months) Fischer 344 rats on the Morris watermaze and the W-maze spatial alternation tasks. Aged rats exhibited impaired performance on both the spatial and spatial working memory components of the tasks relative to young animals. Following acquisition of the spatial alternation task, rats were surgically implanted with dual-bundle hyperdrives that simultaneously recorded electrophysiological signals from the prelimbic and infralimbic regions of the mPFC and the CA1 regions of the intermediate and ventral HC (ivHC) during the spatial alternation task. Robust theta was observed in both the mPFC and ivHC of young and aged rats during task completion. When evaluating theta coherence between the mPFC and ivHC, we found that young rats had greater synchrony when making the correct spatial choice compared to the incorrect choice. In contrast, no correlation between task performance and theta coherence was observed in aged rats. These results indicate that aged rats may rely less on hippocampal-prefrontal circuits during complex spatial navigation and instead engage alternative pathways for task completion, or alternatively, may use oscillations at different frequencies to synchronize between these regions.Release after 04/13/202