Aß Facilitates LTD at Schaffer Collateral Synapses Preferentially in the Left Hippocampus
File Type:
PDFItem Type:
Journal ArticleDate:
2018Access:
openAccessCitation:
O'Riordan, K.J., Hu, N. & Rowan, M.J. Aß Facilitates LTD at Schaffer Collateral Synapses Preferentially in the Left Hippocampus, 2018, Cell Reports, 22, 8Download Item:
1-s2.0-S2211124718301499-main.pdf (PDF) 2.906Mb
Abstract:
Promotion of long-term depression (LTD) mechanisms by synaptotoxic soluble oligomers of amyloid-β (Aß) has been proposed to underlie synaptic dysfunction in Alzheimer’s disease (AD). Previously, LTD was induced by relatively non-specific electrical stimulation. Exploiting optogenetics, we studied LTD using a more physiologically diffuse spatial pattern of selective pathway activation in the rat hippocampus in vivo. This relatively sparse synaptic LTD requires both the ion channel function and GluN2B subunit of the NMDA receptor but, in contrast to electrically induced LTD, is not facilitated by boosting endogenous muscarinic acetylcholine or metabotropic glutamate 5 receptor activation. Although in the absence of Aß, there is no evidence of hippocampal LTD asymmetry, in the presence of Aß, the induction of LTD is preferentially enhanced in the left hippocampus in an mGluR5-dependent manner. This circuit-selective disruption of synaptic plasticity by Aß provides a route to understanding the development of aberrant brain lateralization in AD.
URI:
https://www.sciencedirect.com/science/article/pii/S2211124718301499?via%3Dihubhttp://hdl.handle.net/2262/89893
Sponsor
Grant Number
Science Foundation Ireland
14/IA/2571
Author's Homepage:
http://people.tcd.ie/mrowanType of material:
Journal ArticleURI:
https://www.sciencedirect.com/science/article/pii/S2211124718301499?via%3Dihubhttp://hdl.handle.net/2262/89893
Series/Report no:
Cell Reports;22;
8;
Availability:
Full text availableKeywords:
Synaptic plasticity, Alzheimer's disease, Long-term depression (LTD), Cortical asymmetry, Brain lateralization, Amyloid-β protein, N-methyl-D-aspartate receptor, GluN2B subunit, Metabotropic glutamate 5 receptor, Muscarinic acetylcholine receptorDOI:
http://dx.doi.org/10.1016/j.celrep.2018.01.085Licences: