Send to

Choose Destination
Nat Commun. 2014 Mar 4;5:3374. doi: 10.1038/ncomms4374.

mGlu5 receptors and cellular prion protein mediate amyloid-β-facilitated synaptic long-term depression in vivo.

Author information

Department of Pharmacology and Therapeutics, and Trinity College Institute of Neuroscience, Biotechnology Building, Trinity College Dublin, Dublin 2, Ireland.
Medical Research Council Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Laboratory for Neurodegenerative Research, Center for Neurologic Diseases, Brigham & Women's Hospital, Harvard Institute of Medicine, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.


NMDA-type glutamate receptors (NMDARs) are currently regarded as paramount in the potent and selective disruption of synaptic plasticity by Alzheimer's disease amyloid β-protein (Aβ). Non-NMDAR mechanisms remain relatively unexplored. Here we describe how Aβ facilitates NMDAR-independent long-term depression of synaptic transmission in the hippocampus in vivo. Synthetic Aβ and Aβ in soluble extracts of Alzheimer's disease brain usurp endogenous acetylcholine muscarinic receptor-dependent long-term depression, to enable long-term depression that required metabotropic glutamate-5 receptors (mGlu5Rs). We also find that mGlu5Rs are essential for Aβ-mediated inhibition of NMDAR-dependent long-term potentiation in vivo. Blocking Aβ binding to cellular prion protein with antibodies prevents the facilitation of long-term depression. Our findings uncover an overarching role for Aβ-PrP(C)-mGlu5R interplay in mediating both LTD facilitation and LTP inhibition, encompassing NMDAR-mediated processes that were previously considered primary.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center