Notice: Users may be experiencing issues with displaying some pages on stanfordhealthcare.org. We are working closely with our technical teams to resolve the issue as quickly as possible. Thank you for your patience.
 

Learn about the flu shot, COVID-19 vaccine, and our masking policy »

Stanford Health Care

Chronic Optogenetic Activation Augments A beta Pathology in a Mouse Model of Alzheimer Disease CELL REPORTS Yamamoto, K., Tanei, Z., Hashimoto, T., Wakabayashi, T., Okuno, H., Naka, Y., Yizhar, O., Fenno, L. E., Fukayama, M., Bito, H., Cirrito, J. R., Holtzman, D. M., Deisseroth, K., Iwatsubo, T. 2015; 11 (6): 859-865

Abstract

In vivo experimental evidence indicates that acute neuronal activation increases Aß release from presynaptic terminals, whereas long-term effects of chronic synaptic activation on Aß 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 Aß42 levels immediately after acute light activation. Five months of chronic optogenetic stimulation increased Aß 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 Aß pathology. These findings implicate functional abnormalities of specific neuronal circuitry in Aß pathology and Alzheimer disease.

View details for DOI 10.1016/j.celrep.2015.04.017

View details for Web of Science ID 000354406900002

View details for PubMedID 25937280