Herman Moreno
SUNY Downstate, New York USA
Title: Neuronal Excitability Changes Produced by Alzheimer’s Related Pathology and by Its Risk Factors
Biography
Biography: Herman Moreno
Abstract
Statement of the Problem. Alzheimer’s disease (AD) is characterized by synaptic dysfunction early in the progression of the disease. It remains unknown the specific neuronal abnormalities produced by AD related pathology (amyloid and tau) to the entorhinal cortex (EC)-hippocampus circuit, the region targeted earliest by AD. Here we address this issue by studying mice that express mutated human amyloid precursor protein (hAPP) or mutated human tau protein (hTau) or both in the EC. This approach allowed us to investigate the two pathologies separately and together Additionally we also studied mice expressing the main genetic risk factor for AD (APOE4) .Mice (APOE4) were compared to those expressing APOE3. The experiments showed that expression of mutant hAPP in EC (EC-hAPP) produced a significant increase in the duration of spontaneous extracellular field potentials in the superficial layers of both Medial EC and Lateral EC. We also observed that in EC-hAPP mice, pyramidal neurons of the subiculum, which are monosynaptically excited by EC layer III/II neurons, showed miniature excitatory postsynaptic currents having reduced amplitude, suggesting that the increased excitation observed in EC induced a compensatory negative feedback in subicular projection neurons, a process known as synaptic homeostasis. Modeling of the EC-hippocampus microcircuits indicates that EC hyperexcitability and subicular synaptic downscaling of mice expressing hAPP could be explained by EC interneuron pruning.