© Ed Boyden, 2010
Controlling Brain Circuits with Light
Ed Boyden
© 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
© Ed Boyden, 2010
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
© Ed Boyden, 2010
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’
© Ed Boyden, 2010
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.
© Ed Boyden, 2010
Optical "ber arrays: perturbing brain circuits in 3-D
(photo credit Justin Keena, Keenaphoto.com)
Bernstein et al., in preparation
© Ed Boyden, 2010
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)
© Ed Boyden, 2010
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
© Ed Boyden, 2010
Synthetic neurobiology: creating brain co-processors
Collect data Real-time data mining
Reaction and intelligencePerturbation
© Ed Boyden, 2010
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.
© Ed Boyden, 2010
Pre-clinical safety testing
Han et al., 2009 Neuron 62(2):191-198.Collaboration with labs of Bob Desimone, Ann Graybiel.
© Ed Boyden, 2010
Example: solving a neural disorder, blindness
Rd1AAV10x
© Ed Boyden, 2010
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.
© Ed Boyden, 2010
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.
© Ed Boyden, 2010
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
