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.

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

2. The brain circuits that generate thought,
feeling, consciousness, and action
Lewis et al.
2005
Ramon y Cajal
1899
100,000,000,000 neurons
© Ed Boyden, 2010

3. Treating disorders of the brain via targeted
neuromodulation
1-2 billion worldwide people suffer from:
stroke
addiction
chronic pain
anxiety disorders
blindness
deafness >100,000 people with cochlear
epilepsy implants
Parkinson’s >50,000 with deep brain stimulators
Alzheimer’s tens of thousands with spinal
… stimulators and other stimulators
© Ed Boyden, 2010

4. Why control neural activity?
Testing causality/sufficiency
of neural activity
Re-programming corrupted
neural computations
Cell-type speci c, steerable,
and temporally-precise
+
+ ++ +
+ +
+
+
+ ‘spike’
50 µm 50 µm
© Ed Boyden, 2010

5. A blue light gated ion channel Nagel et al., 2003;
Boyden et al. (2005) Nature Neuroscience 8(9):1263-8.
Channelrhodopsin-2 (ChR2): in green alga
Blue light opens up a pore to let in + charge
Use virus to target to specific neuron types
© Ed Boyden, 2010

6. Optical ber arrays: perturbing brain circuits
in 3-D
Bernstein et al., in preparation
(photo credit Justin Keena, Keenaphoto.com)
© Ed Boyden, 2010

7. Principles of neural control: driving prefrontal cortex to suppress
fear (PTSD model)
x3 X10 (in 5 blocks of 2 trials each)
Tone Tone
Shock
Light
(500 ms train of 125 Hz blue-light pulses (4 ms each),
starting 100 ms after tone onset)
Bernstein, Baratta, et al., in
preparation (collaboration with Ki
Ann Goosens)
© Ed Boyden, 2010

8. Optical neural silencing: screening ecological
and genomic diversity
Han and Boyden 2007, PLos ONE 2(3):e299
Chow, Han, et al., Nature 463:98-102
© Ed Boyden, 2010

9. Synthetic neurobiology: creating brain co-
processors
Collect data Real-time data mining
Reaction and
Perturbation
intelligence
© Ed Boyden, 2010

10. A potential clinical path
Adeno-associated
viruses (AAV):
>600 people in 48
clinical trials,
without a single
serious adverse
event due to the
virus
Firing Rate (Hz)
60 µV
100 µs
Time (ms)
Han et al., 2009 Neuron 62(2):191-198.
Collaboration with labs of Bob Desimone, Ann Graybiel.
© Ed Boyden, 2010

11. Pre-clinical safety testing
Han et al., 2009 Neuron 62(2):191-198.
Collaboration with labs of Bob Desimone, Ann Graybiel.
© Ed Boyden, 2010

12. Example: solving a neural disorder,
blindness
Rd1
AAV
10x
© Ed Boyden, 2010

13. 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

14. 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

15. Collaborators
on projects described
Graduate Students, Postdocs, Staff, and Volunteers Christoph Borgers
Michael Baratta Roderick Bronson
Jake Bernstein
Undergraduate Students Bob Desimone
Brian Chow
Allison Dobry Clif Fonstad
Amy Chuong
August Dietrich Ashutosh Singhal Ki Ann Goosens
Alex Guerra Stephanie Chan Bill Hauswirth
Mike Henninger Alan Horsager
Xue Han Nancy Kopell
Nathan Klapoetke Fiona LeBeau
Emily Ko http://syntheticneurobiology.org/protocols
Yingxi Lin
Patrick Monahan Ed Boyden, esb@media.mit.edu Chris Moore
Al Strelzoff
Ann Graybiel
Giovanni Talei Franzesi
Christian Wentz Alapakkam Sampath
Aimei Yang Patrick Stern
Anthony Zorzos Miles Whittington
Alumni: Mingjie Li, Xiaofeng Qian
Funding
Blindness Project Benesse Foundation; Jerry and Marge Burnett; U.S. Department of Defense;
Ben Matteo, Jian Wen Liu, Cyrus Arman, Ken Digital Life and Things That Think Consortia; Human Frontiers Science Program;
Greenberg 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;
Primate Project NIH Director’s New Innovator Award (1DP2OD002002); NIH (1R43NS070453,
Members of Desimone Lab: Hui-Hui Zhou 1RC2DE020919, 1RC1MH088182, 1R01NS067199, ); NSF (EFRI0835878,
Members of Graybiel Lab: Henry Hall, Pat Harlen DMS0848804); Alfred P. Sloan Foundation; Society for Neuroscience Research
Award for Innovation in Neuroscience (RAIN); Wallace H. Coulter Foundation
© Ed Boyden, 2010