Technological Innovations in Neuroscience Awards

Henry Lester, Ph.D., California Institute of Technology
Ion Channels for Neuronal Engineering
Lester will use ion channels and receptors to gain insight into how neurons are connected within circuits and how such circuits control behavior. He will engineer new receptor channels that respond only to a drug, ivermectin, that can be delivered in an animal’s diet. Once these receptors are developed, it will be possible to study how activating or inhibiting selected neurons influences behavior.

Charles M. Lieber, Ph.D., Harvard University
Nanoelectronic Device Arrays for Electrical and Chemical Mapping of Neural Networks
Lieber plans to develop and demonstrate new nanotechnology-enabled electrophysiology tools to measure electrical and biochemical signaling at the scale of natural synapses, using samples ranging from cultured neural networks to brain tissue. In the long term, these tools may be used as powerful new interfaces between the brain and neural prosthetic devices in biomedical research and, ultimately, treatment.

Fernando Nottebohm, Rockefeller University
Development of a Technique for Making Transgenic Songbirds
The study of vocal learning in songbirds provides an excellent way to explore how memories are stored in a complex brain and how damage to the central nervous system can be repaired by neuronal replacement. Nottebohm seeks to develop a protocol for efficient production of transgenic songbirds in order to test the involvement that individual genes might have in learning and brain repair.

Dalibor Sames, Ph.D., and David Sulzer, Ph.D., Columbia University
Development of Fluorescent False Neurotransmitters: Novel Probes for Direct Visualization of Neurotransmitter Release from Individual Presynaptic Terminals
Sames and Sulzer have developed Fluorescent False Neurotransmitters (FFN) that act as optical tracers of dopamine and enable the first means to optically image neurotransmission at individual synapses. Applying FFNs, Sames and Sulzer will develop new optical methods to examine the synaptic changes associated with learning as well as pathological processes relevant to neurological and psychiatric disorders such as Parkinson’s disease and schizophrenia.

Paul Brehm, Ph.D., Oregon Health & Science University
A novel green fluorescent protein from echinoderms provides a long-term record of neuronal network activity
Brehm is exploring a new way to image cellular activity in healthy and diseased tissue. He proposes an alternative to the jellyfish green fluorescent protein—the bioluminescent brittlestar Ophiopsila, whose long-lasting fluorescence in nerve cells can provide a long-term history of their cellular activity.

Timothy Holy, Ph.D., Washington University School of Medicine
High-speed three-dimensional optical imaging of neural activity in intact tissue
Holy is developing optical methods for recording simultaneously from very large populations of neurons by using thin sheets of light that quickly scan brain tissue in three dimensions. If successful, the study may help scientists observe pattern recognition and learning at the cellular level.

Krisha Shenoy, Ph.D., Stanford University
HermesC: A continuous neural recording system for freely behaving primates
Shenoy's lab is trying to learn more about how neurons act by developing a miniature, head-mounted, high-quality recording system for use on monkeys going about their everyday activities. If successful, this work will create a recording device that can track individual neurons in behaving monkeys for days and weeks.

Gina Turrigiano, Ph.D., Brandeis University
Mapping the position of synaptic proteins using super-resolution fluorescence cryo-microscopy
Turrigiano and her collaborator, David DeRosier, Ph.D., will develop tools to map the way synaptic proteins are arranged into molecular machines that can generate memories and cognitive functions. If this proves successful, they will eventually be able to determine how synapses become disorganized in disease states.

Pamela M. England, Ph.D., University of California at San Francisco
Monitoring AMPA Receptor Trafficking in Real Time
The England lab will develop a novel set of molecular tools, based on synthetic derivatives of philanthotoxin, that could be used to study the cell surface trafficking of the AMPA subtype of glutamate receptor. The goal is to produce a set of toxin derivatives that will inactivate AMPA receptors with specific subunit compositions, thus enabling pharmacological investigation of the role of these different classes of AMPA receptors in living neurons.

Alan Jasanoff, Ph.D., Massachusetts Institute of Technology
Cellular-Level Functional MRI with Calcium Imaging Agents
Jasanoff will explore a novel method of functional Magnetic Resonance Imaging (fMRI), developed in his lab, based on iron oxide nanoparticles that produce image contrast when they aggregate. If successful, the new method will be a more direct measure of neural activity, with the potential for improved spatial and temporal resolution in fMRI.

Richard J. Krauzlis, Ph.D., and Edward M. Callaway, Ph.D., The Salk Institute for Biological Studies
Using Viral Vectors to Probe Sensory-Motor Circuits in Behaving Non-human Primates
Krauzlis and Callaway will develop a method to inactivate specific subpopulations of neurons in localized regions of the monkey cerebral cortex. If successful, their method will provide a means to assess how specific subpopulations of neurons in different brain regions function in circuits to enable higher brain functions, such as perception, memory and sensory-motor control.

Markus Meister, Ph.D., Harvard University
Wireless recording of multi-neuronal spike trains in freely moving animals
Meister and his collaborators, Alan Litke of the University of California, Santa Cruz, and Athanassios Siapas of Caltech, will engineer a wireless microelectrode system that will allow the recording of neural electrical signals from freely moving animals without wires attached. Combining technologies for miniaturization and lightweight materials, this system should facilitate the measurement of neural dynamics during truly natural behaviors, such as burrowing, climbing or flying.

Karl Deisseroth, M.D., Ph.D., Stanford University
Noninvasive, High Temporal Resolution Control of Neuronal Activity Using a Light-Sensitive Ion Channel from the Alga C. Reinhardtii
Deisseroth's lab, including postdoctoral fellow collaborator Edward Boyden, will develop a new tool, based on a genetically encoded light sensitive ion channel from algae, to stimulate electrical activity in specific sets of neurons with light. Their goal is to stimulate individual action potentials with millisecond time precision and to control what neurons are stimulated using genetic methods to target channel protein expression.

Samie R. Jaffrey, M.D., Ph.D., Weill Medical College, Cornell University
Real-time Imaging of RNA in Living Neurons Using Conditionally Fluorescent Small Molecules
Jaffrey's lab will further develop a system to enable visualization of RNA using live-cell fluorescence microscopy. His technique is based on the construction of short RNA sequences that bind to a fluorophore and greatly increase its light emission. The fluorophore is derived from that used in Green Fluorescent Protein (GFP). The goal is to revolutionize the study of RNA in the same way that GFP technology has revolutionized protein visualization.

Jeff W. Lichtman, M.D., Ph.D., Harvard University Kenneth Hayworth, University of Southern California
Development of an Automatic Tape-collecting Lathe-Ultramicrotome for Large-scale Brain Reconstruction
Hayworth and Lichtman are developing a tool to slice and automatically collect thousands of tissue sections for imaging via transmission electron microscopy (TEM). TEM serial section reconstruction is the only technology proven capable of mapping out, at the finest level of resolution, the exact synaptic connectivity of all the neurons within a volume of brain tissue. But application is limited because the ultrathin sections have to be collected manually. This tool would automate the process, making serial sectioning accessible to many labs and useful on larger tissue volumes.

Alice Y. Ting, Ph.D., Massachusetts Institute of Technology
Imaging Neuronal Protein Trafficking by Optical and Electron Microscopy Using Biotin Ligase Labeling
Ting proposes an improved technology to visualize and quantify membrane protein trafficking. She has developed a highly selective enzyme-based labeling technique by which to distinguish molecules existing on neuron surfaces before a stimulus from those appearing after the stimulus. The spatial distribution of labeled molecules can then be observed with optical imaging and, with some modifications, can also be seen in higher resolution with electron microscopy.