Network-Level Characterization of Spontaneous Calcium Activity in an In-Vitro Alzheimer's Disease Model

Abstract

The neurodegenerative disorder Alzheimers disease (AD) is widely known for biomarkers such as amyloid beta plaques and tauopathy, as well as functional differences in memory and cognitive ability. Despite this devastating functional impact, a large body of work only focuses on molecular biomarkers of AD. In this study, we investigate collective neural dynamics in vitro and assess how network-level properties differ between a well-established model of familial AD (FAD) and a newly developed in vitro accelerated model (acAD). The new model system reliably develops the key structural characteristics of AD in three weeks, but its calcium dynamics had not been characterized previously. Spontaneous network dynamics influences information processing as part of the internal network state. Here we measure this spontaneous activity of a network of hundreds of cells in each field of view. We find that the FAD model has a larger fraction of hyperactive cells, while the acAD model displays similar characteristics to healthy cells. Additionally, the FAD model has altered cooperation between cells, losing a proportion of highly correlated cellular activities, both for fast and slow coupling among cells. The acAD model is again consistent with healthy networks. Since the acAD model does not show the same spontaneous network dysfunction seen in FAD, it can enable measurements of changes in learning and memory associated with the plasticity, rather than the structure of the internal network state.