CHARACTERIZING INTRINSIC AGE-RELATED DIFFERENCES IN THE CIRCUIT RESPONSIBLE FOR SPATIAL WORKING MEMORY

Abstract

As the population of individuals aged 65 and older continues to expand worldwide, it becomes increasingly important to characterize the physiological changes associated with the aging process, especially with regards to brain health and cognitive function. Spatial working memory, a complex cognitive process important to navigation, has proven to be exceptionally vulnerable to age-related cognitive decline (Kapellusch et. al, 2018). In this study we aimed to identify differences in the activity of the hippocampal-prefrontal circuit, which is responsible for spatial working memory, across young and old age groups in order to characterize intrinsic changes to this circuit which occur with age. To do this, a biphasic stimulation probe was used to deliver pulses to the ventral and intermediate hippocampus of anesthetized male F344 rats. Evoked potentials in the mPFC were then recorded along the dorsoventral axis (including the infralimbic and prelimbic layers) using a neuropixels 2.0 probe. When comparing the evoked activity in the medial prefrontal cortex in response to ventral hippocampal stimulation between young and old rats, we found that younger rats exhibited more total active neurons and more spiking activity per neuron compared to their older counterparts. These results were shown to be directly related to hippocampal stimulation. Overall, these results suggest that age-dependent physiological changes to the hippocampal-prefrontal projection may underlie observed age-related differences in spatial working memory capability.