Ion channels and neurotransmitter receptors are amongst the most important molecules in the nervous system. They support the high-speed physiological processes that enable neurons to function, they are implicated in many neurological and psychiatric disorders, and they present an incredibly important set of drug targets for treating these diseases. In order to enable a better understanding of how specific ion channels and receptors contribute to behaviors and pathologies, we propose to engineer a toolbox of fully genetically encoded reagents that, when expressed in specific neurons in the brain, enable specific ion channels and ionotropic neurotransmitter receptors to be driven or blocked in a temporally precise fashion, using pulses of light. We anticipate that these tools will find widespread use in both basic and clinical neuroscience, and in other fields of biology, for revealing the roles that specific ion channels and receptors (or changes in their activity levels) play in neural computations, behaviors, and disease states, and for revealing more specific drug targets.

Public Health Relevance

Ion channels and neurotransmitter receptors are molecules that are implicated in a diversity of neurological and psychiatric disorders, and are targets for many important drugs. In order to understand how the modulation of ion channels and receptors might alter the complex circuitry of the brain, we will develop a set of tools that enable selective perturbation of these molecules in targeted cells within the brain. By revealing which cells are most likely to be modulated by a given drug, our technology will enable the development of better drugs with fewer side effects, revealing principles for designing future therapies.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Special Emphasis Panel (ZNS1-SRB-B (26))
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Silberberg, Shai D
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Massachusetts Institute of Technology
Other Domestic Higher Education
United States
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Glantz, Spencer T; Carpenter, Eric J; Melkonian, Michael et al. (2016) Functional and topological diversity of LOV domain photoreceptors. Proc Natl Acad Sci U S A 113:E1442-51
Adamala, Katarzyna P; Martin-Alarcon, Daniel A; Boyden, Edward S (2016) Programmable RNA-binding protein composed of repeats of a single modular unit. Proc Natl Acad Sci U S A 113:E2579-88
Harrison, Reid R; Kolb, Ilya; Kodandaramaiah, Suhasa B et al. (2015) Microchip amplifier for in vitro, in vivo, and automated whole cell patch-clamp recording. J Neurophysiol 113:1275-82
Schmidt, Daniel; Tillberg, Paul W; Chen, Fei et al. (2014) A fully genetically encoded protein architecture for optical control of peptide ligand concentration. Nat Commun 5:3019
Hochbaum, Daniel R; Zhao, Yongxin; Farhi, Samouil L et al. (2014) All-optical electrophysiology in mammalian neurons using engineered microbial rhodopsins. Nat Methods 11:825-33
Chuong, Amy S; Miri, Mitra L; Busskamp, Volker et al. (2014) Noninvasive optical inhibition with a red-shifted microbial rhodopsin. Nat Neurosci 17:1123-9
Klapoetke, Nathan C; Murata, Yasunobu; Kim, Sung Soo et al. (2014) Independent optical excitation of distinct neural populations. Nat Methods 11:338-46
Glaser, Joshua I; Zamft, Bradley M; Marblestone, Adam H et al. (2013) Statistical analysis of molecular signal recording. PLoS Comput Biol 9:e1003145
Kodandaramaiah, Suhasa B; Boyden, Edward S; Forest, Craig R (2013) In vivo robotics: the automation of neuroscience and other intact-system biological fields. Ann N Y Acad Sci 1305:63-71
Chow, Brian Y; Han, Xue; Boyden, Edward S (2012) Genetically encoded molecular tools for light-driven silencing of targeted neurons. Prog Brain Res 196:49-61

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