Cell Reports
Volume 22, Issue 8, 20 February 2018, Pages 2053-2065
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Article
Aß Facilitates LTD at Schaffer Collateral Synapses Preferentially in the Left Hippocampus

https://doi.org/10.1016/j.celrep.2018.01.085Get rights and content
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Highlights

  • Diffuse optical low-frequency stimulation induces LTD at CA3-CA1 synapses in vivo

  • oLTD requires the GluN2B subunit and ion channel function of the NMDA receptor

  • oLTD is not facilitated by boosting acetylcholine or mGlu5 receptor activation

  • At left CA3-CA1 synapses, Aß facilitates oLTD that now needs mGluR5

Summary

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.

Keywords

synaptic plasticity
long-term depression
Alzheimer’s disease
cortical asymmetry
brain lateralization
amyloid-β protein
N-methyl-D-aspartate receptor
GluN2B subunit
metabotropic glutamate 5 receptor
muscarinic acetylcholine receptor

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