Recording and data analysis technologies for observing and analyzing neural circuit dynamics
The brain is a three-dimensional, densely-wired circuit that computes via large sets of widely distributed neurons interacting at fast timescales. In order to understand the brain, ideally it would be possible to observe the activity of many neurons with as great a degree of precision as possible, so as to understand the neural codes and dynamics that are produced by the circuits of the brain. And, ideally, it would be possible to understand how those neural codes and dynamics emerge from the molecular, genetic, and structural properties of the cells making up the circuit. Our lab and our collaborators are developing a number of innovations to enable such analyses of neural circuit dynamics. These tools will hopefully enable pictures of how neurons work together to implement brain computations, and how these computations go awry in brain disorder states. Such neural observation strategies may also serve as detailed biomarkers of brain disorders or indicators of potential drug side effects. We have developed strategies for fMRI mapping, in the awake mouse brain, the neural circuits downstream of optical control of a defined cell type (opto-fMRI) - enabling not only surveys of entire neural circuits to be performed, but for translational bridges to be built between animal and human, enabling interpretation of human brain mapping data in the context of causally mapped mouse neural circuits. We have also developed robotic methods for automated intracellular recording of neurons in the living brain, which uniquely enables the characterizing of synaptic and ion channel influences on neural computation with single-cell resolution. Such technologies may, in conjunction with optogenetics, enable closed-loop neural control technologies, which can introduce information into the brain as a function of brain state ("brain co-processors"), enabling new kinds of circuit characterization tool as well as new kinds of advanced brain-repair prosthetic.
Marblestone, A. H., Zamft, B. M., Maguire, Y. G., Shapiro, M. G., Cybulski, T. R., Glaser, J. I., Amodei, D., Stranges, P. B., Kalhor, R., Dalrymple, D. A., Seo, D., Alon, E., Maharbiz, M. M., Carmena, J. M., Rabaey, J. M., Boyden, E. S.*, Church, G. M. *, Kording, K. P. * (2013) Physical Principles for Scalable Neural Recording, Frontiers in Computational Neuroscience, 7:137. (* equal contribution)
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I. Kolb, G. Holst, B. Goldstein, S.B. Kodandaramaiah, E.S. Boyden, E. Culurciello, C.R. Forest (2013) Automated, in-vivo, whole-cell electrophysiology using an integrated patch-clamp amplifier, Proceedings of the 22nd Annual Computational Neuroscience Meeting (CNS 2013), Paris, France, July 13-18, 2013.
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Zamft, B. M.*, Marblestone, A. H.*, Kording, K., Schmidt, D., Martin-Alarcon, D., Tyo, K., Boyden, E. S., Church, G. (2012) Measuring Cation Dependent DNA Polymerase Fidelity Landscapes by Deep Sequencing, PLoS ONE 7(8): e43876. (* co-first authors)
Kodandaramaiah, S., Talei Franzesi, G., Chow, B., Boyden, E. S.*, Forest, C.* (2012) Automated whole-cell patch clamp electrophysiology of neurons in vivo, Nature Methods 9:585–587. (* co-corresponding authors)
Kodandaramaiah, S., Krijnen, M., Go, J., Malik, S., Sondej, N., Khatait, J. P., Boyden, E. S., Aarts, R. G. K. M., Brouwer, D. M., Forest, C. F. (2011) Characterization of translation of fused silica micropipettes in non-rectilinear trajectories, Proceedings of the 26th Annual Meeting of the American Society for Precision Engineering, Denver, CO.
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)