This proposal seeks to establish essential core research facilities to meet the following identified shared needs of the Stanford Neuroscience research community: (1) gene vector and virus production, (2) advanced microscopy data acquisition and analysis, and (3) automated behavioral phenotyping. Viral vectors are used to express recombinant proteins and/or knock down expression of endogenous proteins in specific subsets of cells in brain tissue. It is even possible to express proteins that enable precise temporal control over the activity of individual neurons. Use of such viral tools is revolutionizing neuroscience research. A centralized core facility will vastly improve the efficiency and cost-effectiveness of virus production. Three dimensional image analysis and visualization are essential for quantifying information from volume imaging techniques, such as Array Tomography, and single- and two-photon confocal microscopy. Software and hardware for this type of analysis is expensive, and has a steep learning curve. This proposal will fund the Image Analysis Center, a central resource with technical expertise to assist scientists with image analysis problems, and an electrophysiological recording setup for an existing shared two-photon tissue slice rig. Standardized, replicable behavioral tests are critical to translating progress from basic neuroscience research to treatments relevant to human disease. Automated behavioral phenotyping can provide more consistent results by eliminating stress due to removal from the home cage and novelty effects from the test environment. Automated testing can also Improve throughput and reduce costs. This proposal will provide funds to expand capacity for automated behavioral testing in an existing core facility. These core facilities will be a central part of SINTN's effort to advance our understanding of normal brain and spinal cord function at the molecular, cellular, and neural circuit level, and to elucidate the pathological processes underlying malfunction of the nervous system following injury or neurologic and psychiatric diseases. Creating core services to meet these shared research needs will foster efficiency and productivity by minimizing the unnecessary duplication of equipment and creating a centralized source of expertise for shared tasks with the net effect of better solutions in less time. Moreover, the resulting formal and informal collaborations will provide the foundation for a richer, stronger, and more vibrant research community.

Public Health Relevance

This proposal will establish core research facilities for use by Stanford Neuroscience faculty. These facilities will enable researchers to more rapidly assess the functions of specific proteins involved in brain disease, brain development, or recovery from brain injury, and provide the means to assess functional changes in individual neuronal cells, in circuits made from groups of cells, and in the behavior of laboratory animals.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Center Core Grants (P30)
Project #
5P30NS069375-03
Application #
8386995
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Talley, Edmund M
Project Start
2011-03-01
Project End
2015-11-30
Budget Start
2012-12-01
Budget End
2013-11-30
Support Year
3
Fiscal Year
2013
Total Cost
$736,297
Indirect Cost
$280,322
Name
Stanford University
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Kramer, Nicholas J; Haney, Michael S; Morgens, David W et al. (2018) CRISPR-Cas9 screens in human cells and primary neurons identify modifiers of C9ORF72 dipeptide-repeat-protein toxicity. Nat Genet 50:603-612
Li, Shi-Bin; Nevárez, Natalie; Giardino, William J et al. (2018) Optical probing of orexin/hypocretin receptor antagonists. Sleep 41:
Liu, Qing; Van Bortle, Kevin; Zhang, Yue et al. (2018) Disruption of mesoderm formation during cardiac differentiation due to developmental exposure to 13-cis-retinoic acid. Sci Rep 8:12960
Razavi, Mehdi; Thakor, Avnesh S (2018) An oxygen plasma treated poly(dimethylsiloxane) bioscaffold coated with polydopamine for stem cell therapy. J Mater Sci Mater Med 29:54
Giardino, William J; Eban-Rothschild, Ada; Christoffel, Daniel J et al. (2018) Parallel circuits from the bed nuclei of stria terminalis to the lateral hypothalamus drive opposing emotional states. Nat Neurosci 21:1084-1095
Bennett, F Chris; Bennett, Mariko L; Yaqoob, Fazeela et al. (2018) A Combination of Ontogeny and CNS Environment Establishes Microglial Identity. Neuron 98:1170-1183.e8
Wilson, Katheryne E; Bachawal, Sunitha V; Willmann, Jürgen K (2018) Intraoperative Resection Guidance with Photoacoustic and Fluorescence Molecular Imaging Using an Anti-B7-H3 Antibody-Indocyanine Green Dual Contrast Agent. Clin Cancer Res 24:3572-3582
Bui, Anh D; Nguyen, Theresa M; Limouse, Charles et al. (2018) Dentate gyrus mossy cells control spontaneous convulsive seizures and spatial memory. Science 359:787-790
Sun, Lu O; Mulinyawe, Sara B; Collins, Hannah Y et al. (2018) Spatiotemporal Control of CNS Myelination by Oligodendrocyte Programmed Cell Death through the TFEB-PUMA Axis. Cell 175:1811-1826.e21
Razavi, Mehdi; Hu, Sophia; Thakor, Avnesh S (2018) A collagen based cryogel bioscaffold coated with nanostructured polydopamine as a platform for mesenchymal stem cell therapy. J Biomed Mater Res A 106:2213-2228

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