1. Neuronal excitation/inhibition imbalance: core element of a translational perspective on Alzheimer pathophysiology
- Author
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Maestú, F., De Haan, W. P., Busche, M.A., DeFelipe, Javier, Dementia Research Institute (UK), Medical Research Council (UK), Ministerio de Ciencia e Innovación (España), and Cajal Blue Brain
- Subjects
Excitation/inhibition imbalance ,Hypersynchronization ,Functional networks ,Microscale ,Computational neuroscience ,Amyloid protein ,Tau protein ,Hyperexcitability ,Meso scale ,Alzheimer’s disease ,Animal models ,Macro scale - Abstract
Our incomplete understanding of the link between Alzheimer's Disease pathology and symptomatology is a crucial obstacle for therapeutic success. Recently, translational studies have begun to connect the dots between protein alterations and deposition, brain network dysfunction and cognitive deficits. Disturbance of neuronal activity, and in particular an imbalance in underlying excitation/inhibition (E/I), appears early in AD, and can be regarded as forming a central link between structural brain pathology and cognitive dysfunction. While there are emerging (non-)pharmacological options to influence this imbalance, the complexity of human brain dynamics has hindered identification of an optimal approach. We suggest that focusing on the integration of neurophysiological aspects of AD at the micro-, meso- and macroscale, with the support of computational network modeling, can unite fundamental and clinical knowledge, provide a general framework, and suggest rational therapeutic targets. M.A.B. is supported by the UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the Medical Research Council, Alzheimer’s Society and Alzheimer Research UK (UKDRI1010). M.A.B. is also funded by a UK RI Future Leaders Fellowship (MR/S017003/1) and a grant from the right Focus Foundation (A2019112S). F.M is supported by the Spanish Minister of Science (RTI2018-098762-B-C31), University of Texas Houston Research Staff grant, NIH− HCP (Connectomics of Aging Brain and Dementia). J.dF was supported by Centro de Investigacion ´ en Red sobre Enfermedades Neurodegenerativas (CIBERNED, CB06/05/0066, Spain); theSpanish “Ministerio de Ciencia e Innovacion´ ”(grant PGC2018-094307-B-I00 and the Cajal Blue Brain Project [the Spanish partner of the Blue Brain Project initiative from EPFL, Switzerland]).
- Published
- 2021