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Metaplasticity mechanisms restore plasticity and associativity in an animal model of Alzheimer's disease.
Li, Qin Navakkode, Sheeja Rothkegel, Martin Soong, Tuck Wah Sajikumar, Sreedharan Korte, Martin
Li, Qin
Navakkode, Sheeja
Rothkegel, Martin
Soong, Tuck Wah
Sajikumar, Sreedharan
Korte, Martin
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Issue Date
2017-05-23
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Abstract
Dynamic regulation of plasticity thresholds in a neuronal population is critical for the formation of long-term plasticity and memory and is achieved by mechanisms such as metaplasticity. Metaplasticity tunes the synapses to undergo changes that are necessary prerequisites for memory storage under physiological and pathological conditions. Here we discovered that, in amyloid precursor protein (APP)/presenilin-1 (PS1) mice (age 3-4 mo), a prominent mouse model of Alzheimer's disease (AD), late long-term potentiation (LTP; L-LTP) and its associative plasticity mechanisms such as synaptic tagging and capture (STC) were impaired already in presymptomatic mice. Interestingly, late long-term depression (LTD; L-LTD) was not compromised, but the positive associative interaction of LTP and LTD, cross-capture, was altered in these mice. Metaplastic activation of ryanodine receptors (RyRs) in these neurons reestablished L-LTP and STC. We propose that RyR-mediated metaplastic mechanisms can be considered as a possible therapeutic target for counteracting synaptic impairments in the neuronal networks during the early progression of AD.
Citation
Metaplasticity mechanisms restore plasticity and associativity in an animal model of Alzheimer's disease. 2017, 114 (21):5527-5532 Proc. Natl. Acad. Sci. U.S.A.
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PubMed Central ID
PMC5448214
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Article
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en
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1091-6490