TY - JOUR
TI - Human Tau isoform-specific presynaptic deficits in a Drosophila Central Nervous System circuit
AU - Kadas, D.
AU - Papanikolopoulou, K.
AU - Xirou, S.
AU - Consoulas, C.
AU - Skoulakis, E.M.C.
JO - Neurobiology of Disease
PY - 2019
VL - 124
TODO - null
SP - 311-321
PB - Academic Press Inc.
SN - 0969-9961, 1095-953X
TODO - 10.1016/j.nbd.2018.12.004
TODO - adult;  age;  article;  central nervous system;  cholinergic synapse;  Drosophila;  human;  nonhuman;  presynaptic nerve;  stimulus;  velocity;  animal;  central nervous system;  Drosophila;  female;  interneuron;  metabolism;  motoneuron;  pathology;  pathophysiology;  physiology;  synapse;  tauopathy;  transgenic animal, isoprotein;  tau protein, Animals;  Animals, Genetically Modified;  Central Nervous System;  Drosophila;  Female;  Humans;  Interneurons;  Motor Neurons;  Protein Isoforms;  Synapses;  tau Proteins;  Tauopathies
TODO - Accumulation of normal or mutant human Tau isoforms in Central Nervous System (CNS) neurons of vertebrate and invertebrate models underlies pathologies ranging from behavioral deficits to neurodegeneration that broadly recapitulate human Tauopathies. Although some functional differences have begun to emerge, it is still largely unclear whether normal and mutant Tau isoforms induce differential effects on the synaptic physiology of CNS neurons. We use the oligosynaptic Giant Fiber System in the adult Drosophila CNS to address this question and reveal that 3R and 4R isoforms affect distinct synaptic parameters. Whereas 0N3R increased failure rate upon high frequency stimulation, 0N4R compromised stimulus conduction and response speed at a specific cholinergic synapse in an age-dependent manner. In contrast, accumulation of the R406W mutant of 0N4R induced mild, age-dependent conduction velocity defects. Because 0N4R and its mutant isoform are expressed equivalently, this demonstrates that the defects are not merely consequent of exogenous human Tau accumulation and suggests distinct functional properties of 3R and 4R isoforms in cholinergic presynapses. © 2018
ER -