Amyloid-b as a positive endogenous regulator of release probability at hippocampal synapses (Nat Neurosci, 2009, 12:1567-1576)

報告日期: 2010/06/11
報告時間: 15:10/16:00
報告學生: 施耀翔
講評老師: 許桂森

Amyloid-β as a positive endogenous regulator of

release probability at hippocampal synapses

Nature Neuroscience, December ( 2009) , vol.12, 1567–1576


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


Speaker: Yao-Hsiang Shih

Advisor: Dr. Kuei-Sen, Hsu

Date: 2010/06/11

Room: 602 教室



Accumulation of cerebral amyloid-β peptide (Aβ) is essential for developing synaptic and cognitive deficits in Alzheimer’s disease. The production and subsequent release of Aβ positively correlate with the level of neuronal and synaptic activity. It has been suggested that synaptic vesicle recycling through coupled endo-exocytosis is the primary mechanism that mediates activity dependent Aβ production and release. Synapse loss is the strongest structural correlate of cognitive decline in patients with Alzheimer’s disease. The ectopic application of specific Aβ peptides has generated highly heterogeneous data, ranging from an increase in spontaneous synaptic activity and intrinsic excitability of neurons to a lack of effect on synaptic transmission or even its depression. However, the physiological functions of Aβ, as well as the primary mechanisms that initiate early Aβ-mediated synaptic dysfunctions, remain largely unknown. And it is still not understood how endogenously released Aβ, comprising peptides of different lengths and molecular conformations, regulates synaptic transfer in normal, non-transgenic hippocampal circuits on a fast timescale. In this study, the authors used optical and electrophysiological tools to assess the acute effects of changes in endogenous extracellular Aβ concentration on synaptic transmission during different patterns of neuronal activity in rat hippocampal cultures and in acute hippocampal slices. And the data shows that endogenously released Aβ peptides positively regulate the release probability of synapses, but do not alter postsynaptic function or intrinsic neuronal excitability. 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.