Abstract WP234: Age And Type 2 Diabetes Reduce The Coherence Of Theta And Gamma Oscillations Between Brain Networks

Introduction: The integrity of the functional connectivity across networks relies on synchronous activation of neurons, which reduces with age. Type 2 diabetes (T2DM) is a major risk factor for stroke and cognitive decline and also a precocious aging, yet the electrophysiological changes in T2DM and its interaction with aging is not well understood. The current study sought to delineate the age and diabetic effect on the resting state field potential in regions crucial for cognition. Methods: Local field potential was recorded under urethane anesthesia with multichannel electrodes spanning the cortex and hippocampus (HPC) in control (db/+) and diabetic (db/db) mice, at 200 or 400 days of age. Brain state and neural activity in signal power of δ, θ, γ waves and sharp-wave associated ripples (SWRs) were determined. Coherence and phase-amplitude coupling (PAC) within the HPC or between cortex and HPC were computed to reflect the level of functional communication across brain networks. Results: Our results show that age decreased the θ/δ amplitude (T/D) ratio and the signal power of the theta, gamma and high gamma in the cortex and the HPC. Both age and diabetes prolonged the average duration of SWR clusters and inter-ripple intervals. The greatest SWR signal power was detected in db/db mice at 200 ds of age compared to the other 3 groups, so were the γ power in the cortex and HPC during SWRs. Both age and diabetes reduced θ coherence between cortex and HPC. Age also reduced γ coherence within the hippocampus. Interestingly, while age reduced the coherence of high γ band between hippocampus and CTX, diabetes significantly increased it. To the contrary, age increased coherence in δ within the hippocampal layers. Diabetes decreased the θ-low γ PAC between CA1 and cortex and within CA1. However, diabetes increased δ-γ PAC within the slm, while both age and diabetes increased the δ-γ PAC between the hippocampus and the cortex. Conclusion: The neural activity and synchrony in brain regions crucial for cognitive function is impaired by age and further confounded by T2DM. The perturbation of resting state field potential signal power and coherence may underlie age and diabetes induced loss of functional connectivity and cognitive decline.