English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Beta amyloid (Aβ) triggers the elimination of excitatory synaptic connections in the CNS, an early manifestation of Alzheimer's disease. Oligomeric assemblies of Aβ peptide associate with excitatory synapses resulting in synapse elimination through a process that requires NMDA-type glutamate receptor activation. Whether Aβ affects synaptic NMDA receptor (NMDAR) function directly and acts locally at synapses to which it has bound and whether synaptic activity influences Aβ synaptic binding and synaptotoxicity have remained fundamental questions. Here, we used subcellular Ca 2+ imaging in rat hippocampal neurons to visualize NMDAR function at individual synapses before and after Aβ application. Aβ triggered a robust impairment of NMDAR Ca 2+ entry at most, but not all, synapses. NMDAR function was more severely impaired at highly active synapses and synapses with bound Aβ, but activity was not required for Aβ synapse binding. Blocking NMDARs during Aβ exposure prevented Aβ-mediated impairment. Finally, Aβ impaired NMDAR Ca 2+ entry at doses much lower than those required for NMDAR internalization, revealing a novel, potent mode of NMDAR regulation by Aβ.

Local and Use-Dependent Effects of β-Amyloid Oligomers on NMDA Receptor Function Revealed by Optical Quantal Analysis