Aß Facilitates LTD at Schaffer Collateral Synapses Preferentially in the Left Hippocampus

Cell Reports
Kenneth J O'RiordanM J Rowan

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.

Citations

Aug 21, 2019·Brain and Behavior·Yahan WangZhenhong Liu
Apr 7, 2020·Reviews in the Neurosciences·Diana Marcela Cuestas Torres, Fernando P Cardenas
May 29, 2020·The European Journal of Neuroscience·Andrea Moreno
Aug 13, 2021·Molecular Neurobiology·Malte KlüssendorfHans-Jürgen Kreienkamp

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