Abstract：
:In vivo experimental evidence indicates that acute neuronal activation increases Aβ release from presynaptic terminals, whereas long-term effects of chronic synaptic activation on Aβ pathology remain unclear. To address this issue, we adopted optogenetics and transduced stabilized step-function opsin, a channelrhodopsin engineered to elicit a long-lasting neuronal hyperexcitability, into the hippocampal perforant pathway of APP transgenic mice. In vivo microdialysis revealed a ∼24% increase in the hippocampal interstitial fluid Aβ42 levels immediately after acute light activation. Five months of chronic optogenetic stimulation increased Aβ burden specifically in the projection area of the perforant pathway (i.e., outer molecular layer of the dentate gyrus) of the stimulated side by ∼2.5-fold compared with that in the contralateral side. Epileptic seizures were observed during the course of chronic stimulation, which might have partly contributed to the Aβ pathology. These findings implicate functional abnormalities of specific neuronal circuitry in Aβ pathology and Alzheimer disease.
journal_name
Cell Repjournal_title
Cell reportsauthors
Yamamoto K,Tanei ZI,Hashimoto T,Wakabayashi T,Okuno H,Naka Y,Yizhar O,Fenno LE,Fukayama M,Bito H,Cirrito JR,Holtzman DM,Deisseroth K,Iwatsubo Tdoi
10.1016/j.celrep.2015.04.017subject
Has Abstractpub_date
2015-05-12 00:00:00pages
859-865issue
6issn
2211-1247pii
S2211-1247(15)00404-0journal_volume
11pub_type
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