Abstract - Anne Andrews

The brain possesses the most complex chemistry encountered in living systems. While methods exist to measure neurotransmitter signaling in the extraneuronal space, spatial, temporal, and chemical resolution is limited. To investigate intra-neuronal signaling at the length and time scales pertinent to intrinsically encoded information, and ultimately to relate this information to complex behavior, chemically specific sensors are needed that approach the size of synapses (ca. 20 nm) having sub-second response times. The objective of this proposal is to employ recently developed, broadly applicable approaches to identify sensing elements that selectively recognize neurotransmitters. Neurotransmitter-functionalized self-assembled monolayer substrates, high-throughput microfluidics, and next-generation sequencing will be used to distinguish high-affinity molecular recognition elements screened from nucleic acid combinatorial libraries (aptamer selection). Our long-range goals are to develop the next generation of in vivo neurotransmitter sensors that will be ultra-small (nanoscale), fast (<1 s), and multiplexed for simultaneous neurotransmitter measurements. In the future, when linked to semiconductor nanowires, neurotransmitter-specific aptamers will be interrogated for their potential to act as brain biosensors. Near-term gains include creating a library of high-affinity neurotransmitter aptamers. Broader impact will be a greater understanding of the neurochemical basis of complex behavior, psychiatric and neurodegenerative disorders, and the treatment of these disorders.

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AWARDS

Principal Investigator Institution Title Abstract
Andersen, Richard California Institute of Technology Engineering Artificial Sensation View
Andrews, Anne University of California, Los Angeles Nanoscale Neurotransmitter Sensors View
Bloodgood, Brenda University of California San Diego A novel toolkit for visualizing and manipulating activity-induced transcription in living brain. View
Chaumeil, Myriam University of California, San Francisco In vivo metabolic imaging of neuroinflammation using hyperpolarized 13C View
Cleary, Michael University of California, Merced Capturing physiological maps of neural gene expression View
Cohen, Bruce University of California, Lawrence Berkeley National Laboratory Nano-optogenetic control of neuronal firing with targeted nanocrystals View
Dai, Hongjie Stanford University  Deep brain imaging of single neurons in the second near-infrared optical window View
Hall, Drew University of California, San Diego Magnetic Monitoring of Neural Activity using Magnetoresistive Nanosensors View
Krubitzer, Leah University of California, Davis An integrated system to monitor, image, and regulate neural activity View
Kubby, Joel University of California, Santa Cruz Three-Photon Microscopy with Adaptive Optics for Deep Tissue Brain Activity Imaging View
Melosh, Nicholas Stanford University Parallel Solid State Intracellular Patch-Clamping with Biomimetic Probes View
Park, B. Hyle University of California, Riverside  Label-free 4D optical detection of neural activity View
Portera-Cailliau, Carlos University of California, Los Angeles High-speed interrogation of network activity with frequency domain multiplexing View
Shanechi, Maryam University of Southern California Control-Theoretic Neuroprosthetic Design Using Electrocorticography Signals View
Smith, Will University of California, Santa Barbara Whole brain imaging in a primative chordate View
Wood, Marcelo University of California, Irvine Epigenetic PET tracer for cross-species investigation of age-related memory dysfunction View