To support pursuit of the NINDS mission, here we propose to introduce a high-impact novel technology for Imaging to the Washington University Neuroscience community. We intend to provide Core Instrumentation to perform Planar Illumination Microscopy (also known as light sheet microscopy) to catalyze new imaging efforts that aim to monitor large-scale neuronal ensembles. The recent Federal announcement of the Brain Activity Map targets neurophysiology for rapid growth and development in the coming decade. One of the most promising techniques for high-throughput neurophysiology is fluorescence imaging using light sheets. Our implementation, Objective-Coupled Planar Illumination (OCPI) microscopy, achieves imaging speeds that are hundreds or thousands of times faster than two-photon microscopy by simultaneously illuminating all pixels in the objective's focal plane, thereby eliminating the need to collect images by scanning one pixel at a time. The method achieves fast imaging simultaneously with high sensitivity and low phototoxicity and is therefore particularly well-suited to long-term recording periods. The custom-built OCPI instrument will be a Core offering within an existing Imaging Center, the Bakewell Neurolmaging Facility. Therefore, this proposal describes a plan and a schedule by which the new OCPI microscope will be introduced, and the oversight we will establish to ensure that its use is made available fairly and broadly. We also emphasize that we have recent experience in precisely these community-based efforts: we successfully introduced earlier version of this instrumentation as a Core facility and now can foresee the need for more access by a larger community of Neuroscientists to a faster and more flexible version. We plan Facility support for OCPI users that includes a facility manager to provide maintenance and training, a data center for image analysis, and a data manager to help with customized data analysis. We provide a series of quantifiable milestones by which to evaluate progress in offering this new high-impact technology.'By the end of the 4-yr period, we anticipate a steady base of at least 20 different users from across the diverse WU Neuroscience community, and a usage rate at or near full-time.

Public Health Relevance

We will use NINDS support to provide Core Instrumentation for a new imaging modality to monitor large-scale neuronal ensembles. These efforts will catalyze discoveries across a broad spectrum of neuroscience research, and promote the NINDS mission to reduce the burden of neurological disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Resource-Related Research Projects (R24)
Project #
1R24NS086741-01
Application #
8662909
Study Section
Special Emphasis Panel (ZNS1-SRB-B (38))
Program Officer
Talley, Edmund M
Project Start
2014-03-01
Project End
2018-02-28
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
1
Fiscal Year
2014
Total Cost
$608,124
Indirect Cost
$41,778
Name
Washington University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Murali, Bhavna; Ren, Qihao; Luo, Xianmin et al. (2018) Inhibition of the Stromal p38MAPK/MK2 Pathway Limits Breast Cancer Metastases and Chemotherapy-Induced Bone Loss. Cancer Res 78:5618-5630
Kim, Joanna; Cooper, John A (2018) Septins regulate junctional integrity of endothelial monolayers. Mol Biol Cell 29:1693-1703
Betleja, Ewelina; Nanjundappa, Rashmi; Cheng, Tao et al. (2018) A novel Cep120-dependent mechanism inhibits centriole maturation in quiescent cells. Elife 7:
Wildburger, Norelle C; Gyngard, Frank; Guillermier, Christelle et al. (2018) Amyloid-? Plaques in Clinical Alzheimer's Disease Brain Incorporate Stable Isotope Tracer In Vivo and Exhibit Nanoscale Heterogeneity. Front Neurol 9:169
Song, Wilbur M; Joshita, Satoru; Zhou, Yingyue et al. (2018) Humanized TREM2 mice reveal microglia-intrinsic and -extrinsic effects of R47H polymorphism. J Exp Med 215:745-760
Li, Lucy X; Rautengarten, Carsten; Heazlewood, Joshua L et al. (2018) UDP-Glucuronic Acid Transport Is Required for Virulence of Cryptococcus neoformans. MBio 9:
Hoye, Mariah L; Koval, Erica D; Wegener, Amy J et al. (2017) MicroRNA Profiling Reveals Marker of Motor Neuron Disease in ALS Models. J Neurosci 37:5574-5586
Liang, Xitong; Holy, Timothy E; Taghert, Paul H (2017) A Series of Suppressive Signals within the Drosophila Circadian Neural Circuit Generates Sequential Daily Outputs. Neuron 94:1173-1189.e4
Sakers, Kristina; Lake, Allison M; Khazanchi, Rohan et al. (2017) Astrocytes locally translate transcripts in their peripheral processes. Proc Natl Acad Sci U S A 114:E3830-E3838
Lo, Hei-Yong G; Jin, Ramon U; Sibbel, Greg et al. (2017) A single transcription factor is sufficient to induce and maintain secretory cell architecture. Genes Dev 31:154-171

Showing the most recent 10 out of 16 publications