Soluble Aβ Oligomers Impair Dipolar Heterodendritic Plasticity by Activation of mGluR in the Hippocampal CA1 Region

• Published in: iScience Vol. 6; pp. 138 - 150
• Main Authors: Zhao, Jianhua, Li, Anna, Rajsombath, Molly, Dang, Yifan, Selkoe, Dennis J., Li, Shaomin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 31.08.2018; Elsevier
• Subjects: Cellular Neuroscience; Disease; Neuroscience; Disease; Neuroscience; Cellular Neuroscience
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2018.07.018

Soluble Aβ oligomers (oAβs) contribute importantly to synaptotoxicity in Alzheimer disease (AD), but the mechanisms related to heterogeneity of synaptic functions at local circuits remain elusive. Nearly all studies of the effects of oAβs on hippocampal synaptic plasticity have only examined homosynaptic plasticity. Here we stimulated the Schaffer collaterals and then simultaneously recorded in stratum radiatum (apical dendrites) and stratum oriens (basal dendrites) of CA1 neurons. We found that the apical dendrites are significantly more vulnerable to oAβ-mediated synaptic dysfunction: the heterosynaptic basal dendritic long-term potentiation (LTP) remained unchanged, whereas the homosynaptic apical LTP was impaired. However, the heterosynaptic basal dendritic plasticity induced by either spaced 10-Hz bursts or low-frequency (1-Hz) stimulation was disrupted by oAβs in a mGluR5-dependent manner. These results suggest that different firing patterns in the same neurons may be selectively altered by soluble oAβs in an early phase of AD, before frank neurodegeneration. [Display omitted] •Soluble Aβ oligomers have little effect on heterodendritic basal dendritic LTP•Soluble Aβ oligomers facilitate both basal and apical dendritic LTD induction•Stimulation timing determines the oAβ impairment of heterosynaptic basal LTP•Basal dendrites are less sensitive to Aβ oligomer-mediated synaptotoxicity Neuroscience; Cellular Neuroscience; Disease