Controlling Brain Circuits with Light

   Ed Boyden




© Ed Boyden, 2010
The brain circuits that generate thought,
                  feeling, consciousness, and action




                       ...
Treating disorders of the brain via targeted
                            neuromodulation

          1-2 billion worldwide ...
Why control neural activity?
                              Testing causality/sufficiency
                                 of...
A blue light gated ion channel                   Nagel et al., 2003;
                                  Boyden et al. (2005...
Optical ber arrays: perturbing brain circuits
                                       in 3-D
                       Bernste...
Principles of neural control: driving prefrontal cortex to suppress
                                    fear (PTSD model)
...
Optical neural silencing: screening ecological
                      and genomic diversity




      Han and Boyden 2007, ...
Synthetic neurobiology: creating brain co-
                                   processors

                      Collect da...
A potential clinical path
          Adeno-associated
            viruses (AAV):
          >600 people in 48
            cl...
Pre-clinical safety testing




                         Han et al., 2009 Neuron 62(2):191-198.
                         C...
Example: solving a neural disorder,
                                blindness




                                      Rd...
Authors: Mehdi Doroudchi1,7, Jian Wen Liu2,7, Kimberly A. Silka3, Edward S. Boyden1,4, Kenneth P. Greenberg1,5,
      Jenn...
Authors: Mehdi Doroudchi1,7, Jian Wen Liu2,7, Kimberly A. Silka3, Edward S. Boyden1,4, Kenneth P. Greenberg1,5,
      Jenn...
Collaborators
                                                                                                    on proje...
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Controlling Brain Circuits With Light - Ed Boyden - H+ Summit @ Harvard

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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.

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

  1. 1. Controlling Brain Circuits with Light Ed Boyden © Ed Boyden, 2010
  2. 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. 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. 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. 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. 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. 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. 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. 9. Synthetic neurobiology: creating brain co- processors Collect data Real-time data mining Reaction and Perturbation intelligence © Ed Boyden, 2010
  10. 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. 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. 12. Example: solving a neural disorder, blindness Rd1 AAV 10x © Ed Boyden, 2010
  13. 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. 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. 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
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