Abstract - Michael Cleary

Altered gene expression is an understudied feature of activity-dependent neuromodulation that can tune or even change neural circuits. Standard methods for measuring brain activity detect biochemical or metabolic changes that provide information that is complimentary to transcription profiles. Our technology will allow context-dependent transcription profiles to be overlayed on connectome maps and incorporated into behavioral studies. In this technique, non-invasive delivery of a nucleotide precursor is coupled to behaviors known to involve neuromodulation (e.g. drug addiction, learning). The nucleotide precursor is only incorporated into nascent mRNAs in neurons or glia engineered to express a combination of nucleotide salvage enzymes that are absent from metazoans. Our method provides significantly greater specificity and sensitivity than currently available techniques. During the pilot year, we will optimize and validate this technology using the invertebrate model Drosophila melanogaster. Work in Drosophila will allow activity-dependent transcription responses to be mapped onto well-defined adult brain circuits. This technology is easily scalable to other systems and in future years will be applied to studies in the mouse brain. Ultimately, data derived from this technology is likely to provide new markers of brain function in humans and a deeper understanding of contextdependent brain physiology.

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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