Independent two-color optogenetic excitation of neural populations

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 2013.

Bibliographic Details
Main Author: Klapoetke, Nathan Cao
Other Authors: Edward S. Boyden, III.
Format: Thesis
Language:eng
Published: Massachusetts Institute of Technology 2014
Subjects:
Online Access:http://hdl.handle.net/1721.1/86285
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author Klapoetke, Nathan Cao
author2 Edward S. Boyden, III.
author_facet Edward S. Boyden, III.
Klapoetke, Nathan Cao
author_sort Klapoetke, Nathan Cao
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description Thesis: Ph. D., Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 2013.
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spelling mit-1721.1/862852019-04-09T16:17:24Z Independent two-color optogenetic excitation of neural populations Klapoetke, Nathan Cao Edward S. Boyden, III. Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences. Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences. Brain and Cognitive Sciences. Thesis: Ph. D., Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 2013. Cataloged from PDF version of thesis. Includes bibliographical references (pages 104-106). The optical modulation of neurons with channelrhodopsins, a class of genetically encoded light-gated ion channels, has enabled the spatiotemporally precise interrogation of the roles individual cell types play in neural circuit dynamics. A topic of great interest to the neuroscience community is the independent optical excitation of two distinct neuron populations with different wavelengths, which would enable the interrogation of emergent phenomena such as circuit dynamics, plasticity, and neuromodulation. Previous implementations have focused on maximizing spectral separation by driving one channelrhodopsin in the violet (405 nm) and the other in the yellow (590 nm), yet it has not been possible to achieve independent violet excitation without eliciting spikes from both populations, due to the intrinsic UV-blue light sensitivity of the retinal chromophore. This thesis designs and implements an improved two-color excitation scheme where effective light sensitivity is utilized to achieve independent optical excitation in blue (470 nm) and red (625 nm) channels. Zero post-synaptic crosstalk is demonstrated in acute murine slice, using two novel channeirhodopsins identified from a systematic screen of 80 naturally occurring, previously uncharacterized opsins in primary neuron culture. Gene88 is the first known yellow-peaked channelrhodopsin, with a peak 45 nm more red-shifted than any previous channelrhodopsin, while Gene90 has the fastest channel turn on, turn off, and recovery kinetics of any known channelrhodopsin. These opsins' novel properties enable the first known demonstration of post-synaptic crosstalk-free two-color excitation with temporally precise modulation of spatially inseparable neuron populations. by Nathan Cao Klapoetke. Ph. D. 2014-04-25T15:49:04Z 2014-04-25T15:49:04Z 2013 2013 Thesis http://hdl.handle.net/1721.1/86285 876050440 eng M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 106 pages application/pdf Massachusetts Institute of Technology
spellingShingle Brain and Cognitive Sciences.
Klapoetke, Nathan Cao
Independent two-color optogenetic excitation of neural populations
title Independent two-color optogenetic excitation of neural populations
title_full Independent two-color optogenetic excitation of neural populations
title_fullStr Independent two-color optogenetic excitation of neural populations
title_full_unstemmed Independent two-color optogenetic excitation of neural populations
title_short Independent two-color optogenetic excitation of neural populations
title_sort independent two color optogenetic excitation of neural populations
topic Brain and Cognitive Sciences.
url http://hdl.handle.net/1721.1/86285
work_keys_str_mv AT klapoetkenathancao independenttwocoloroptogeneticexcitationofneuralpopulations