Optogenetic hardware and systems for control of neural circuits and biological functions with light
The brain is a densely wired, heterogeneous circuit made out of perhaps thousands of different kinds of cells. Over the last several years we have developed a set of "optogenetic" reagents, fully genetically encoded reagents that, when targeted to specific cells, enable their physiology to be controlled via light. To confront the 3-dimensional complexity of the living brain, enabling the analysis of the circuits that causally drive or support specific neural computations and behaviors, our lab and our collaborators have developed hardware for delivery of light into the brain, enabling control of complexly shaped neural circuits, as well as the ability to combinatorially activate and silence neural activity in distributed neural circuits. These technologies, including microfabricated arrays of waveguides that can deliver light into the brain in a 3-D fashion, wirelessly powered and controlled arrays of LEDs coupled to optical fibers, technologies for activating and silencing neurons in an MRI-compatible fashion, and others, are opening up the ability to discover, or screen for in a high-throughput fashion, new neural targets that can serve as candidates for the treatment of brain disorders. We and our collaborators have also developed accessory technologies, such as light-proof neural recording electrodes, and injector arrays capable of delivering viruses encoding for light-activated molecules into multiple sites in the brain. We anticipate that these tools will enable the systematic analysis of the brain circuits that mechanistically and causally contribute to specific behaviors and pathologies. We distribute these tools as freely as is feasible to researchers -- see the "Resources" pages below for up-to- date descriptions of, and the "Publications" pages for detailed designs and examples of, these tools.
Alivisatos, A., Andrews, A., Boyden, E. S., Chun, M., Church, G., Deisseroth, K., Donoghue, J., Fraser, S., Lippincott-Schwartz, J., Looger, L., Masmanidis, S., McEuen, P., Nurmikko, A., Park, H., Peterka, D., Reid, C., Roukes, M., Scherer, A., Schnitzer, M., Sejnowski, T., Shepard, K., Tsao, D., Turrigiano, G., Weiss, P., Xu, C., Yuste, R., Zhuang, X. (2013) Nanotools for Neuroscience and Brain Activity Mapping, ACS Nano, 7(3):1850-66.
Zorzos, A. N., Scholvin, J., Boyden, E. S.*, Fonstad, C. G. (2012) Three-dimensional multiwaveguide probe array for light delivery to distributed brain circuits, Optics Letters 37(23):4841-4843. (* corresponding author)
Bernstein, J. G., Garrity, P. A.*, Boyden, E. S.* (2012) Optogenetics and thermogenetics: technologies for controlling the activity of targeted cells within intact neural circuits, Current Opinion in Neurobiology 22(1):61-71. (* co-corresponding authors)
Doroudchi, M. M., Greenberg, K. P., Zorzos, A. N., Hauswirth, W. W., Fonstad, C. G., Horsager, A., Boyden, E. S. (2011) Towards Optogenetic Sensory Replacement, Conference Proceedings of the IEEE Engineering in Medicine and Biology Society 2011:3139-41.
Wentz, C. T., Bernstein, J. G., Monahan, P., Guerra, A., Rodriguez, A., Boyden, E. S. (2011) A Wirelessly Powered and Controlled Device for Optical Neural Control of Freely-Behaving Animals, Journal of Neural Engineering 8(4):046021.
Doroudchi, M. M., Greenberg, K. P., Liu, J., Silka, K. A., Boyden, E. S., Lockridge, J. A., Arman, A. C., Janani, R., Boye, S. E., Boye, S. L., Gordon, G. M., Matteo, B. C., Sampath, A. P., Hauswirth, W. W., Horsager, A. (2011) Virally delivered Channelrhodopsin-2 Safely and Effectively Restores Visual Function in Multiple Mouse Models of Blindness, Molecular Therapy 19(7):1220-9.
Zorzos, A. N., Boyden, E. S.*, and Fonstad, C. G. (2010) Multiwaveguide implantable probe for light delivery to sets of distributed brain targets, Optics Letters 35(24):4133-5. (* corresponding author)
Desai M., Kahn I., Knoblich U., Bernstein J., Atallah H., Yang A., Kopell, N., Buckner R.L., Graybiel A. M., Moore C. I.*, and Boyden E. S.* (2011) Mapping Brain Networks in Awake Mice Using Combined Optical Neural Control and fMRI, Journal of Neurophysiology 105(3):1393-405. (* co-corresponding authors)
Boyden, E. S., Han, X., Talei Franzesi, G., Chan, S., Bernstein, J., Qian, X., Li, M. (2009) "New Techniques for Investigating Brain Rhythms: Optical Neural Control and Multielectrode Recording," In: Rhythms of the Neocortex: Where Do They Come From and What Are They Good For? (Kopell N., ed.) pp. 65-75. Washington, DC: Society for Neuroscience.
Han, X.*, Qian, X., Bernstein, J.G., Zhou, H.-H., Talei Franzesi, G., Stern, P., Bronson, R.T., Graybiel, A.M., Desimone, R., and Boyden, E.S.* (2009) Millisecond-Timescale Optical Control of Neural Dynamics in the Nonhuman Primate Brain, Neuron 62(2): 191-198. (* co-corresponding authors)
Bernstein, J. G., Han, X., Henninger, M. A., Ko, E. Y., Qian, X., Franzesi, G. T., McConnell, J. P., Stern, P., Desimone, R., and Boyden, E. S. (2008) Prosthetic systems for therapeutic optical activation and silencing of genetically-targeted neurons, Proc Soc Photo Opt Instrum Eng 6854:68540H.
Wang, H., Peca, J., Matsusaki, M., Matsusaki, K., Noguchi, J., Qiu, L., Wang, D., Zhang, F., Boyden, E. S., Deisseroth, K., Kasai, H., Hall, W. C., Feng, G., Augustine, G. J. (2007) High-speed mapping of synaptic connectivity using photostimulation in channelrhodopsin-2 transgenic mice, Proceedings of the National Academy of Sciences 104(19):8143-848.