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 #
5P30NS069375-02
Application #
8231395
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
2011-12-01
Budget End
2012-11-30
Support Year
2
Fiscal Year
2012
Total Cost
$788,046
Indirect Cost
$301,870
Name
Stanford University
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Goddard, C Alex; Mysore, Shreesh P; Bryant, Astra S et al. (2014) Spatially reciprocal inhibition of inhibition within a stimulus selection network in the avian midbrain. PLoS One 9:e85865
Dimov, Ivan K; Lu, Rong; Lee, Eric P et al. (2014) Discriminating cellular heterogeneity using microwell-based RNA cytometry. Nat Commun 5:3451
Engels, Marc C; Rajarajan, Kuppusamy; Feistritzer, Rebecca et al. (2014) Insulin-like growth factor promotes cardiac lineage induction in vitro by selective expansion of early mesoderm. Stem Cells 32:1493-502
Coutellier, Laurence; Ardestani, Pooneh Memar; Shamloo, Mehrdad (2014) ?1-adrenergic receptor activation enhances memory in Alzheimer's disease model. Ann Clin Transl Neurol 1:348-360
Painter, Michio W; Brosius Lutz, Amanda; Cheng, Yung-Chih et al. (2014) Diminished Schwann cell repair responses underlie age-associated impaired axonal regeneration. Neuron 83:331-43
Portmann, Thomas; Yang, Mu; Mao, Rong et al. (2014) Behavioral abnormalities and circuit defects in the basal ganglia of a mouse model of 16p11.2 deletion syndrome. Cell Rep 7:1077-92
Sharma, Arun; Marceau, Caleb; Hamaguchi, Ryoko et al. (2014) Human induced pluripotent stem cell-derived cardiomyocytes as an in vitro model for coxsackievirus B3-induced myocarditis and antiviral drug screening platform. Circ Res 115:556-66
Ebert, Antje D; Kodo, Kazuki; Liang, Ping et al. (2014) Characterization of the molecular mechanisms underlying increased ischemic damage in the aldehyde dehydrogenase 2 genetic polymorphism using a human induced pluripotent stem cell model system. Sci Transl Med 6:255ra130
He, Yingbo; Zhang, Hui; Yung, Andrea et al. (2014) ALK5-dependent TGF-? signaling is a major determinant of late-stage adult neurogenesis. Nat Neurosci 17:943-52
Fenno, Lief E; Mattis, Joanna; Ramakrishnan, Charu et al. (2014) Targeting cells with single vectors using multiple-feature Boolean logic. Nat Methods 11:763-72

Showing the most recent 10 out of 25 publications