University of Tasmania, Australia

Neuronal activity is determined by the interplay of morphology, synaptic inputs and intrinsic excitability, which varies from neuron to neuron. Subsets of cortical and hippocampal pyramidal neurons are especially vulnerable to degeneration in AD, however, the basis of this selective neuronal vulnerability is unknown. We will use a multidimensional approach to define precisely how neuronal activity is altered in AD in vulnerable groups of neurons: patch-clamp electrophysiology will be used to measure multiple biophysical properties consecutively in individual neurons from transgenic AD mice and wild-type control mice in combination with detailed morphological data from the same recorded neurons. Assessing multiple parameters concurrently, from changes in ion channels in the neuronal membrane through to structural alterations, will enable us to answer fundamental questions in an animal model that replicates the earliest stage of AD, with the long-term goal of identifying novel combination therapeutics to ameliorate the functional deficits caused by AD.