Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 12 (12), 1567-76

Amyloid-beta as a Positive Endogenous Regulator of Release Probability at Hippocampal Synapses


Amyloid-beta as a Positive Endogenous Regulator of Release Probability at Hippocampal Synapses

Efrat Abramov et al. Nat Neurosci.


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

Similar articles

See all similar articles

Cited by 176 articles

See all "Cited by" articles


    1. J Physiol. 1996 Feb 15;491 ( Pt 1):163-76 - PubMed
    1. Neurosci Lett. 2004 Aug 19;366(3):320-5 - PubMed
    1. Ann Neurol. 1991 Oct;30(4):572-80 - PubMed
    1. J Biol Chem. 2001 Jun 15;276(24):21895-901 - PubMed
    1. Neuron. 1997 Apr;18(4):599-612 - PubMed

Publication types

MeSH terms

LinkOut - more resources