Cognitive Resilience in Aging Degus is Linked to CA3 Hippocampal GABAergic Integrity

Abstract

The preservation of cognitive function during aging remains a key challenge in neuroscience. In this study, we applied an integrative approach, combining behavioral assays with neurophysiological recordings, to investigate hippocampal circuit integrity. We used Octodon degus, a rodent with exceptional longevity (up to 10 years in laboratory conditions), as a natural model of aging and neurodegenerative disease such as Alzheimer. To assess agerelated cognitive changes, we employed three behavioral tasks: Novel Object Recognition (NOR), Open Field (OF), and the Burrowing Test (BT). The BT reflects Activities of Daily Living (ADLs) and is based on species-typical spontaneous burrowing behavior, which has been linked to neurodegenerative markers in degus. We also performed multielectrode electro-physiological recordings to assess GABAergic function in the hippocampus. Aged degus with high BT performance (classified as good burrowers, or GB) showed robust hippocampal activity, especially in the CA3 region, a key hub for signal integration and memory encoding. In contrast, degus with poor BT performance (bad burrowers, or BB) exhibited reduced spontaneous hippocampal activity, suggesting potential compensation via GABA-independent synaptic mechanisms. Altogether, our findings suggest that preserved GABAergic function supports cognitive resilience in aging degus. These results offer new insights into the neural mechanisms underlying healthy cognitive aging and may inform future strategies for preventing or mitigating neurodegeneration.