Controlling Brain Circuits With Light - Ed Boyden - H+ Summit @ Harvard

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© Ed Boyden, 2010 Controlling Brain Circuits with Light Ed Boyden

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Ed Boyden Assistant Professor, MIT Media Lab, MIT Brain and Cognitive Sciences, and MIT Biological Engineering Controlling Brain Circuits with Light The brain is three-dimensional and densely-wired with billions of heterogeneous computational primitives. Understanding how these elements work in real time to mediate behavior and consciousness, and how they are compromised in neural pathology, is a top priority. We have recently revealed methods for real-time optical activation and silencing of specific cell types in the brain, using naturally-occurring molecular sensitizers such as channelrhodopsin-2, halorhodopsin, and archaerhodopsin. Building off of these molecular tools, we also have created optical hardware and algorithms for systematically testing the contribution of brain regions, cell types, and circuit connections to behavioral functions. We are also working on noninvasive methods of information delivery to the brain. We discuss the application of these technologies to the analysis of neural dynamics, as well as to translation for new treatments for human disease, and eventually towards augmentation of the human condition. Ed Boyden is the Benesse Career Development Professor at the MIT Media Lab, assistant professor of Biological Engineering and Brain and Cognitive Sciences at MIT, and leader of the Synthetic Neurobiology Group. His group aims to discover principles for controlling neural circuits in order to understand how cognition and emotion arise, and also to enable systematic repair of intractable brain disorders such as epilepsy, Parkinson's disease, post-traumatic stress disorder, and chronic pain. In order to accomplish this, his group invents new tools for controlling and observing the computations performed by brain circuits. He has launched an award-winning series of classes at MIT that teach principles of neuroengineering, starting with basic principles of how to control and observe neural functions, and culminating with launching companies in the nascent neurotechnology space. He was named to the "Top 35 Innovators Under the Age of 35" by Technology Review in 2006, his lab's work was selected to the Discovery Science Channel's "Top 5 Best Science Moments" in 2007, and he was selected for the "Top 20 Brains Under Age 40" by Discover Magazine in 2008, as well as awarded the NIH Director's New Innovator Award and the Society for Neuroscience Research Award for Innovation in Neuroscience. Ed received his PhD in neurosciences from Stanford University as a Hertz Fellow, where he discovered that the molecular mechanisms used to store a memory are determined by the content to be learned. Before, he received three degrees in electrical engineering and physics from MIT. He has contributed to over 200 papers, current or pending patents, and articles, has given over 80 invited talks, and writes a column for Technology Review magazine.

Transcript of Controlling Brain Circuits With Light - Ed Boyden - H+ Summit @ Harvard

Page 1: Controlling Brain Circuits With Light - Ed Boyden - H+ Summit @ Harvard

© Ed Boyden, 2010

Controlling Brain Circuits with Light

Ed Boyden

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© Ed Boyden, 2010

The brain circuits that generate thought, feeling, consciousness, and action

Ramon y Cajal1899

Lewis et al.2005

100,000,000,000 neurons

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Treating disorders of the brain via targeted neuromodulation

1-2 billion worldwide people suffer from: stroke addiction chronic pain anxiety disorders blindness deafness epilepsy Parkinson’s Alzheimer’s …

>100,000 people with cochlear implants

>50,000 with deep brain stimulatorstens of thousands with spinal

stimulators and other stimulators

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Why control neural activity?Testing causality/sufficiency

of neural activity Re-programming corrupted

neural computationsCell-type speci"c, steerable,

and temporally-precise

50 µm 50 µm

+++

+ + +++

+ +

‘spike’

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A blue light gated ion channel

Channelrhodopsin-2 (ChR2): in green algaBlue light opens up a pore to let in + chargeUse virus to target to specific neuron types

Nagel et al., 2003; Boyden et al. (2005) Nature Neuroscience 8(9):1263-8.

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Optical "ber arrays: perturbing brain circuits in 3-D

(photo credit Justin Keena, Keenaphoto.com)

Bernstein et al., in preparation

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Principles of neural control: driving prefrontal cortex to suppress fear (PTSD model)

ToneShock

x3

Bernstein, Baratta, et al., in preparation (collaboration with Ki Ann Goosens)

Tone

Light

X10 (in 5 blocks of 2 trials each)

(500 ms train of 125 Hz blue-light pulses (4 ms each), starting 100 ms after tone onset)

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Optical neural silencing: screening ecological and genomic diversity

Chow, Han, et al., Nature 463:98-102 Han and Boyden 2007, PLos ONE 2(3):e299

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Synthetic neurobiology: creating brain co-processors

Collect data Real-time data mining

Reaction and intelligencePerturbation

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A potential clinical path

Adeno-associated viruses (AAV):

>600 people in 48 clinical trials, without a single serious adverse event due to the virus

Time (ms)Firin

g R

ate

(Hz)

60 µV

100 µs

Han et al., 2009 Neuron 62(2):191-198.Collaboration with labs of Bob Desimone, Ann Graybiel.

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Pre-clinical safety testing

Han et al., 2009 Neuron 62(2):191-198.Collaboration with labs of Bob Desimone, Ann Graybiel.

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Example: solving a neural disorder, blindness

Rd1AAV10x

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Authors: Mehdi Doroudchi1,7, Jian Wen Liu2,7, Kimberly A. Silka3, Edward S. Boyden1,4, Kenneth P. Greenberg1,5, Jennifer A. Lockridge1, A. Cyrus Arman6, Ramesh Janani1, Gabriel M. Gordon3, Benjamin C. Matteo1, Alapakkam P. Sampath6,8, William W. Hauswirth2,8, Alan Horsager1,3,8,9

 Author Addresses: 1Eos Neuroscience, Inc., Los Angeles, CA; 2Dept. of Ophthalmology, UF, Gainesville, FL; 3Institute for Genetic Medicine, USC, Los Angeles, CA; 4MIT Media Lab, MIT, Cambridge, MA; 5Division of Neurobiology, UC Berkeley, Berkeley, CA; 6Zilhka Neurogenetic Institute, USC, Los Angeles, CA; 7These authors contributed equally; 8These authors contributed equally; 9Corresponding author.

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Authors: Mehdi Doroudchi1,7, Jian Wen Liu2,7, Kimberly A. Silka3, Edward S. Boyden1,4, Kenneth P. Greenberg1,5, Jennifer A. Lockridge1, A. Cyrus Arman6, Ramesh Janani1, Gabriel M. Gordon3, Benjamin C. Matteo1, Alapakkam P. Sampath6,8, William W. Hauswirth2,8, Alan Horsager1,3,8,9

 Author Addresses: 1Eos Neuroscience, Inc., Los Angeles, CA; 2Dept. of Ophthalmology, UF, Gainesville, FL; 3Institute for Genetic Medicine, USC, Los Angeles, CA; 4MIT Media Lab, MIT, Cambridge, MA; 5Division of Neurobiology, UC Berkeley, Berkeley, CA; 6Zilhka Neurogenetic Institute, USC, Los Angeles, CA; 7These authors contributed equally; 8These authors contributed equally; 9Corresponding author.

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Graduate Students, Postdocs, Staff, and VolunteersMichael BarattaJake BernsteinBrian ChowAmy ChuongAugust DietrichAlex GuerraMike HenningerXue HanNathan KlapoetkeEmily KoPatrick MonahanAl StrelzoffGiovanni Talei FranzesiChristian WentzAimei YangAnthony Zorzos

Alumni: Mingjie Li, Xiaofeng Qian

Blindness ProjectBen Matteo, Jian Wen Liu, Cyrus Arman, Ken Greenberg

Primate ProjectMembers of Desimone Lab: Hui-Hui ZhouMembers of Graybiel Lab: Henry Hall, Pat Harlen

Undergraduate StudentsAllison Dobry

Ashutosh SinghalStephanie Chan

Collaborators on projects described

Christoph Borgers Roderick Bronson

Bob DesimoneClif Fonstad

Ki Ann Goosens Bill HauswirthAlan Horsager

Nancy KopellFiona LeBeau

Yingxi LinChris Moore

Ann GraybielAlapakkam Sampath

Patrick SternMiles Whittington

http://syntheticneurobiology.org/protocols Ed Boyden, [email protected]

FundingBenesse Foundation; Jerry and Marge Burnett; U.S. Department of Defense; Digital Life and Things That Think Consortia; Human Frontiers Science Program; McGovern Institute and McGovern Institute Neurotechnology (MINT) Program; MIT Alumni Class Funds; MIT McGovern Institute; MIT Media Lab; MIT Mind-Machine Project; MIT Neurotechnology Fund (& its generous donors); NARSAD; NIH Director’s New Innovator Award (1DP2OD002002); NIH (1R43NS070453, 1RC2DE020919, 1RC1MH088182, 1R01NS067199, ); NSF (EFRI0835878, DMS0848804); Alfred P. Sloan Foundation; Society for Neuroscience Research Award for Innovation in Neuroscience (RAIN); Wallace H. Coulter Foundation