A system for optically controlling neural circuits with very high spatial and temporal resolution

Optogenetics offers a powerful new approach for controlling neural circuits. It has a vast array of applications in both basic and clinical science. For basic science, it opens the door to unraveling circuit operations, since one can perturb specific circuit components with high spatial (single cell) and high temporal (millisecond) resolution. For clinical applications, it allows new kinds of selective treatments, because it provides a method to inactivate or activate specific components in a malfunctioning circuit and bring it back into a normal operating range [1-3]. To harness the power of optogenetics, though, one needs stimulating tools that work with the same high spatial and temporal resolution as the molecules themselves, the channelrhodopsins. To date, most stimulating tools require a tradeoff between spatial and temporal precision and are prohibitively expensive to integrate into a stimulating/recording setup in a laboratory or a device in a clinical setting [4, 5]. Here we describe a Digital Light Processing (DLP)-based system capable of extremely high temporal resolution (sub-millisecond), without sacrificing spatial resolution. Furthermore, it is constructed using off-the-shelf components, making it feasible for a broad range of biology and bioengineering labs. Using transgenic mice that express channelrhodopsin-2 (ChR2), we demonstrate the system's capability for stimulating channelrhodopsin-expressing neurons in tissue with single cell and sub-millisecond precision.

[1]  Gernot Heiser,et al.  An Analysis of Power Consumption in a Smartphone , 2010, USENIX Annual Technical Conference.

[2]  F. Werblin,et al.  Differential Targeting of Optical Neuromodulators to Ganglion Cell Soma and Dendrites Allows Dynamic Control of Center-Surround Antagonism , 2011, Neuron.

[3]  Karl Deisseroth,et al.  Functional Control of Transplantable Human ESC‐Derived Neurons Via Optogenetic Targeting , 2010, Stem cells.

[4]  Murtaza Z Mogri,et al.  Optical Deconstruction of Parkinsonian Neural Circuitry , 2009, Science.

[5]  Patrick Degenaar,et al.  Multi-site optical excitation using ChR2 and micro-LED array , 2010, Journal of neural engineering.

[6]  Patrick Degenaar,et al.  Optobionic vision—a new genetically enhanced light on retinal prosthesis , 2009, Journal of neural engineering.

[7]  Aravinthan D. T. Samuel,et al.  Optogenetic manipulation of neural activity in freely moving Caenorhabditis elegans , 2011, Nature Methods.

[8]  E. Boyden,et al.  Multiple-Color Optical Activation, Silencing, and Desynchronization of Neural Activity, with Single-Spike Temporal Resolution , 2007, PloS one.

[9]  Chethan Pandarinath,et al.  Retinal prosthetic strategy with the capacity to restore normal vision , 2012, Proceedings of the National Academy of Sciences.

[10]  E. Bamberg,et al.  Channelrhodopsin-2, a directly light-gated cation-selective membrane channel , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Michael Z. Lin,et al.  Characterization of engineered channelrhodopsin variants with improved properties and kinetics. , 2009, Biophysical journal.

[12]  Feng Zhang,et al.  An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology , 2007, Journal of neural engineering.

[13]  Douglas S Kim,et al.  Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration , 2008, Nature Neuroscience.

[14]  K. Deisseroth,et al.  Ultrafast optogenetic control , 2010, Nature Neuroscience.

[15]  Matthew M. Crane,et al.  Real-time multimodal optical control of neurons and muscles in freely-behaving Caenorhabditis elegans , 2011, Nature Methods.

[16]  W. C. Hall,et al.  High-speed mapping of synaptic connectivity using photostimulation in Channelrhodopsin-2 transgenic mice , 2007, Proceedings of the National Academy of Sciences.

[17]  Luke Campagnola,et al.  Fiber-coupled light-emitting diode for localized photostimulation of neurons expressing channelrhodopsin-2 , 2008, Journal of Neuroscience Methods.

[18]  Thomas J. Davidson,et al.  Closed-loop optogenetic control of thalamus as a new tool to interrupt seizures after cortical injury , 2012, Nature Neuroscience.

[19]  Sharad Ramanathan,et al.  Optical interrogation of neural circuits in Caenorhabditis elegans , 2009, Nature Methods.

[20]  E. Charbon,et al.  CMOS driven micro-pixel LEDs integrated with single photon avalanche diodes for time resolved fluorescence measurements , 2008 .

[21]  S. Shoham,et al.  Patterned Optical Activation of Retinal Ganglion Cells , 2007, 2007 29th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.