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Proceedings Paper

Optogenetic stimulation of cholinergic projection neurons as an alternative for deep brain stimulation for Alzheimer’s treatment
Author(s): James Mancuso; Yuanxin Chen; Zhen Zhao; Xuping Li; Zhong Xue; Stephen T. C. Wong
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Paper Abstract

Deep brain stimulation (DBS) of the cholinergic nuclei has emerged as a powerful potential treatment for neurodegenerative disease and is currently in a clinical trial for Alzheimer’s therapy. While effective in treatment for a number of conditions from depression to epilepsy, DBS remains somewhat unpredictable due to the heterogeneity of the projection neurons that are activated, including glutamatergic, GABAergic, and cholinergic neurons, leading to unacceptable side effects ranging from apathy to depression or even suicidal behavior. It would be highly advantageous to confine stimulation to specific populations of neurons, particularly in brain diseases involving complex network interactions such as Alzheimer’s. Optogenetics, now firmly established as an effective approach to render genetically-defined populations of cells sensitive to light activation including mice expressing Channelrhodopsin-2 specifically in cholinergic neurons, provides just this opportunity. Here we characterize the light activation properties and cell density of cholinergic neurons in healthy mice and mouse models of Alzheimer’s disease in order to evaluate the feasibility of using optogenetic modulation of cholinergic synaptic activity to slow or reverse neurodegeneration. This paper is one of the very first reports to suggest that, despite the anatomical depth of their cell bodies, cholinergic projection neurons provide a better target for systems level optogenetic modulation than cholinergic interneurons found in various brain regions including striatum and the cerebral cortex. Additionally, basal forebrain channelrhodopsin-expressing cholinergic neurons are shown to exhibit normal distribution at 60 days and normal light activation at 40 days, the latest timepoints observed. The data collected form the basis of ongoing computational modeling of light stimulation of entire populations of cholinergic neurons.

Paper Details

Date Published: 8 March 2013
PDF: 9 pages
Proc. SPIE 8565, Photonic Therapeutics and Diagnostics IX, 85655M (8 March 2013); doi: 10.1117/12.2004379
Show Author Affiliations
James Mancuso, Weill Cornell Medical College (United States)
Yuanxin Chen, Weill Cornell Medical College (United States)
Zhen Zhao, Weill Cornell Medical College (United States)
Southeast Univ. Medical School (China)
Xuping Li, Weill Cornell Medical College (United States)
Zhong Xue, Weill Cornell Medical College (United States)
Stephen T. C. Wong, Weill Cornell Medical College (United States)

Published in SPIE Proceedings Vol. 8565:
Photonic Therapeutics and Diagnostics IX
Andreas Mandelis; Brian Jet-Fei Wong; Anita Mahadevan-Jansen; Henry Hirschberg M.D.; Hyun Wook Kang; Nikiforos Kollias; Melissa J. Suter; Kenton W. Gregory M.D.; Guillermo J. Tearney M.D.; Stephen Lam; Bernard Choi; Steen J. Madsen; Bodo E. Knudsen M.D.; E. Duco Jansen; Justus F. Ilgner M.D.; Haishan Zeng; Matthew Brenner; Laura Marcu, Editor(s)

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