Amyloid-? oligomers suppress subunit-specific glutamate receptor increase during LTP.

ABSTRACT: Introduction:Amyloid-? oligomers (A?Os) 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 A?Os affect excitatory synaptic plasticity remains to be elucidated. Methods:In order to study the effects of A?Os 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 A?Os for 1-2 days inhibited the increase in GluA1 number and GluA1 exocytosis frequency in both postsynaptic and extrasynaptic membranes during LTP. In contrast, A?Os did not inhibit the increase in GluA2 number or exocytosis frequency. Discussion:These results suggest that A?Os primarily inhibit the increase in the number of GluA1 homomers and suppress hippocampal LTP expression.

SUBMITTER: Tanaka H 

PROVIDER: S-EPMC6880111 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature