Amyloid-Β as a positive endogenous regulator of release probability at hippocampal synapses

Efrat Abramov, Iftach Dolev, Hilla Fogel, Giuseppe D. Ciccotosto, Eyal Ruff, Inna Slutsky*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

422 Scopus citations

Abstract

Accumulation of cerebral amyloid-Β peptide (AΒ) is essential for developing synaptic and cognitive deficits in Alzheimer's disease. However, the physiological functions of AΒ, as well as the primary mechanisms that initiate early AΒ-mediated synaptic dysfunctions, remain largely unknown. Here we examine the acute effects of endogenously released AΒ peptides on synaptic transfer at single presynaptic terminals and synaptic connections in rodent hippocampal cultures and slices. Increasing extracellular AΒ by inhibiting its degradation enhanced release probability, boosting ongoing activity in the hippocampal network. Presynaptic enhancement mediated by AΒ was found to depend on the history of synaptic activation, with lower impact at higher firing rates. Notably, both elevation and reduction in AΒ levels attenuated short-term synaptic facilitation during bursts in excitatory synaptic connections. These observations suggest that endogenous AΒ peptides have a crucial role in activity-dependent regulation of synaptic vesicle release and might point to the primary pathological events that lead to compensatory synapse loss in Alzheimer's disease.

Original languageEnglish
Pages (from-to)1567-1576
Number of pages10
JournalNature Neuroscience
Volume12
Issue number12
DOIs
StatePublished - Dec 2009

Funding

FundersFunder number
Charles E. Smith Family
Israel Ministry of Health
National Institute of Psychobiology in Israel
Rosalinde and Arthur Gilbert Foundation
Israel Science Foundation
Center for Nanoscience and Nanotechnology, Tel Aviv University

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