Neural network function in a mouse model of Alzheimer's disease. (360G-Wellcome-086840_Z_08_Z)

A recent revision to the amyloid cascade hypothesis has highlighted the important role played by intermediate AB oligomers in early-stage synaptic and cognitive dysfunction in Alzheimer's Disease 1. This revised hypothesis predicts that the very earliest stages of amyloid-induced cognitive dysfunction are a result of a breakdown in synaptic plasticity processes and the subsequent disruption to neural network activity that encodes and retrieves information 2. However, there has been little or no research carried out to examine how amyloid production influences network activity in murine models of amyloid pathology. The main aim of this proposal is to build upon our preliminary work that shows amyloid production disrupts network activity within the hippocampus and between the hippocampus and key regions contributing to memory. Furthermore we will examine how exercise-induced plasticity in the hippocampus (most notably in the dentate gyrus) influences network properties in APP over expressing mice.