Alzheimer’s-Induced Changes in Grid Cell Electrophysiology Affect Path Integration in a Network Model of the Medial Entorhinal Cortex

Abstract

Alzheimer’s disease (AD) is the leading cause of dementia in the modern day, due to the rapid increase in life expectancy across the developed world. While there is no known cure for AD, a sufficiently early diagnosis can precipitate better outcomes in terms of preserving the quality of life experienced by AD patients. In the earliest stages of AD, studies have reported abnormalities in the electrophysiological properties of neurons in the entorhinal cortex (EC), a region of the brain that plays a crucial role in spatial navigation. In particular, grid cells in the EC have been shown to exhibit altered firing patterns in AD patients. Grid cells are neurons that fire in a spatially periodic manner, and are thought to be responsible for the brain’s ability to form cognitive maps of the environment. Using a biophysically-realistic computational model of the grid cells, we have investigated the effects of varying electrophysiological properties in the EC on the network dynamics of grid cells. Our results show that altering certain electrophysiological properties leads to changes in the spatial periodicity of the grid cells, creating a signature which could potentially be used as a diagnostic tool for AD. While further work is needed to validate these results, our study provides a proof-of-concept for the use of computational models in understanding the pathophysiology of AD.