Open AccessAmyloid‐β oligomers suppress subunit‐specific glutamate receptor increase during LTP
Author(s) -
Tanaka Hiromitsu,
Sakaguchi Daiki,
Hirano Tomoo
Publication year - 2019
Publication title -
alzheimer's and dementia: translational research and clinical interventions
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.49
H-Index - 30
ISSN - 2352-8737
DOI - 10.1016/j.trci.2019.10.003
Subject(s) - long term potentiation , ampa receptor , glutamate receptor , synaptic plasticity , exocytosis , excitatory postsynaptic potential , ltp induction , hippocampal formation , postsynaptic potential , chemistry , neuroscience , microbiology and biotechnology , biology , inhibitory postsynaptic potential , receptor , biochemistry , secretion
Amyloid‐β oligomers (AβOs) are assumed to impair the ability of learning and memory by suppressing the induction of synaptic plasticity, such as long‐term potentiation (LTP) in the early stage of Alzheimer's disease. However, the direct molecular mechanism of how AβOs affect excitatory synaptic plasticity remains to be elucidated. Methods In order to study the effects of AβOs on LTP‐associated changes of AMPA (alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid)‐type glutamate receptor (AMPAR) movement, we performed live‐cell imaging of fluorescently labeled AMPAR subunit GluA1 or GluA2 with total internal reflection fluorescence microscopy. Results Incubation of cultured hippocampal neurons with AβOs for 1–2 days inhibited the increase in GluA1 number and GluA1 exocytosis frequency in both postsynaptic and extrasynaptic membranes during LTP. In contrast, AβOs did not inhibit the increase in GluA2 number or exocytosis frequency. Discussion These results suggest that AβOs primarily inhibit the increase in the number of GluA1 homomers and suppress hippocampal LTP expression.