Award Abstract # 1707356
NeuroNex Technology Hub: Enhanced resolution for 3DEM analysis of synapses across brain regions and taxa

NSF Org: DBI
Division of Biological Infrastructure
Recipient: UNIVERSITY OF TEXAS AT AUSTIN
Initial Amendment Date: July 24, 2017
Latest Amendment Date: July 18, 2023
Award Number: 1707356
Award Instrument: Cooperative Agreement
Program Manager: Reed Beaman
rsbeaman@nsf.gov
 (703)292-7163
DBI
 Division of Biological Infrastructure
BIO
 Directorate for Biological Sciences
Start Date: August 1, 2017
End Date: August 31, 2024 (Estimated)
Total Intended Award Amount: $3,620,000.00
Total Awarded Amount to Date: $9,650,000.00
Funds Obligated to Date: FY 2017 = $1,810,000.00
FY 2018 = $1,810,000.00

FY 2019 = $2,410,000.00

FY 2020 = $1,860,003.00

FY 2021 = $1,759,997.00
History of Investigator:
  • Kristen Harris (Principal Investigator)
    kharris@mail.clm.utexas.edu
  • James Carson (Co-Principal Investigator)
Recipient Sponsored Research Office: University of Texas at Austin
110 INNER CAMPUS DR
AUSTIN
TX  US  78712-1139
(512)471-6424
Sponsor Congressional District: 25
Primary Place of Performance: University of Texas at Austin
TX  US  78759-5316
Primary Place of Performance
Congressional District:
37
Unique Entity Identifier (UEI): V6AFQPN18437
Parent UEI:
NSF Program(s): Cross-BIO Activities,
CESER-Cyberinfrastructure for
Primary Program Source: 01001718DB NSF RESEARCH & RELATED ACTIVIT
01002021DB NSF RESEARCH & RELATED ACTIVIT

01001819DB NSF RESEARCH & RELATED ACTIVIT

01001920DB NSF RESEARCH & RELATED ACTIVIT

01002122DB NSF RESEARCH & RELATED ACTIVIT
Program Reference Code(s): 8091, 8089
Program Element Code(s): 727500, 768400
Award Agency Code: 4900
Fund Agency Code: 4900
Assistance Listing Number(s): 47.074

ABSTRACT

As part of the NSF National Research Infrastructure for Neuroscience, this Neurotechnology Hub will develop new approaches to examine the brain in greater detail. Three-dimensional electron microscopy (3DEM) has helped reveal new insights into the role of tiny connections between cells in the brain. However, 3DEM has been limited in impact by the rate of data analysis. This Neurotechnology Hub will improve the 3DEM instrumentation to collect information in greater detail, develop better algorithms to process the information, and link the workflows with high performance computing to greatly increase the rate of knowledge discovery. These innovations and capabilities will be shared with the scientific community through active training on the approach, and through open access to the new software and data. By way of this Neurotechnology Hub, 3DEM will become part of the national infrastructure for neuroscience research. To help address the grand scientific challenge of understanding the brain, this project will apply the improved 3DEM approach across several different mammalian species including humans to identify similarities and differences, and their relationship to behavior, learning, and memory.

This Neurotechnology Hub is motivated by challenges in understanding synapses, the tiny points of inter-neuronal communication. The variance in synapse dimensions, connectivity, and subcellular content across species is simply not known, yet required to determine whether model systems represent human brain functions. Current approaches are limited by resolution, inefficient data collection, and analysis bottlenecks. Addressing these challenges, the project will: (1) Develop simultaneous multi-detector and tilt-tomography on the scanning electron microscope operating in the transmission mode. Add-on hardware and software will improve axial resolution from 45 to 10 nm (or less), while maintaining in-plane resolution of 1-2 nm. (2) Integrate automated and interactive tools that speed and improve analysis of synapses in large data volumes. The enhanced resolution will increase data volume but reduce major image processing difficulties by producing more isotropic images. (3) Integrate the enhanced electron microscopy (EM) with high performance computing to increase throughput; to disseminate images, metadata, analyses, and software in a way that facilitates uptake into existing cell type and brain databases; and to provide a venue to develop 3DEM communities. (4) Apply the new technology to image hippocampus and comparable parts of cortex in mice, rats, and humans. This NeuroTechnology Hub award is co-funded by the Division of Emerging Frontiers within the Directorate for Biological Sciences and the Office of Advanced Cyberinfrastructure within the Directorate for Computer and Information Sciences, as part of the BRAIN Initiative and NSF's Understanding the Brain activities.

PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH

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(Showing: 1 - 10 of 33)
Mendelsohn, Rachel and Garcia, Guadalupe C. and Bartol, Thomas M. and Lee, Christopher T. and Khandelwal, Priya and Liu, Emily and Spencer, Donald J. and Husar, Adam and Bushong, Eric A. and Phan, Sebastien and Perkins, Guy and Ellisman, Mark H. and Skupi "Morphological principles of neuronal mitochondria" Journal of Comparative Neurology , v.530 , 2022 https://doi.org/10.1002/cne.25254 Citation Details
Ordyan, Mariam and Bartol, Tom and Kennedy, Mary and Rangamani, Padmini and Sejnowski, Terrence "Interactions between calmodulin and neurogranin govern the dynamics of CaMKII as a leaky integrator" PLOS Computational Biology , v.16 , 2020 https://doi.org/10.1371/journal.pcbi.1008015 Citation Details
Ostrovskaya, Olga I. and Cao, Guan and Eroglu, Cagla and Harris, Kristen M. "Developmental onset of enduring longterm potentiation in mouse hippocampus" Hippocampus , v.30 , 2020 https://doi.org/10.1002/hipo.23257 Citation Details
Pharris, Matthew C. and Patel, Neal M. and VanDyk, Tyler G. and Bartol, Thomas M. and Sejnowski, Terrence J. and Kennedy, Mary B. and Stefan, Melanie I. and Kinzer-Ursem, Tamara L. "A multi-state model of the CaMKII dodecamer suggests a role for calmodulin in maintenance of autophosphorylation" PLOS Computational Biology , v.15 , 2019 https://doi.org/10.1371/journal.pcbi.1006941 Citation Details
Ruiz-Martínez, Á. and Bartol, T. M. and Sejnowski, T. J. and Tartakovsky, D. M. "Stochastic self-tuning hybrid algorithm for reaction-diffusion systems" The Journal of Chemical Physics , v.151 , 2019 10.1063/1.5125022 Citation Details
samavat, m "Regional and LTP-Dependent Variation of Synaptic Information Storage Capacity in rat hippocampus" bioRxiv , 2022 Citation Details
Samavat, Mohammad and Bartol, Thomas M and Harris, Kristen M and Sejnowski, Terrence J "Synaptic Information Storage Capacity Measured With Information Theory" Neural Computation , v.36 , 2024 https://doi.org/10.1162/neco_a_01659 Citation Details
Singh, Nishant and Bartol, Thomas and Levine, Herbert and Sejnowski, Terrence and Nadkarni, Suhita "Presynaptic endoplasmic reticulum regulates short-term plasticity in hippocampal synapses" Communications Biology , v.4 , 2021 https://doi.org/10.1038/s42003-021-01761-7 Citation Details
Thiyagarajan, Vijay Venu and Sheridan, Arlo and Harris, Kristen M and Manor, Uri "A deep learning-based strategy for producing dense 3D segmentations from sparsely annotated 2D images" bioRxiv , 2024 https://doi.org/10.1101/2024.06.14.599135 Citation Details
Bell, Miriam and Bartol, Tom and Sejnowski, Terrence and Rangamani, Padmini "Dendritic spine geometry and spine apparatus organization govern the spatiotemporal dynamics of calcium" Journal of General Physiology , v.151 , 2019 10.1085/jgp.201812261 Citation Details
Cailey Bromer, Thomas M. "Long-term potentiation expands information content of hippocampal dentate gyrus synapses" Proceedings of the National Academy of Sciences of the United States of America , 2018 pnas.1716189115 Citation Details
(Showing: 1 - 10 of 33)

PROJECT OUTCOMES REPORT

Disclaimer

This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.

The major goals of this project were to foster the development and dissemination of innovative research resources, instrumentation, and neurotechnologies to better understand the framework of brain function across organization levels, analyses, and wider range of species, including the human brain. The development of our Neurotechnology Hub (3dem.org) provides a centralized, controlled cyberinfrastructure to encompass existing tools for the 3D reconstruction of serial brain images to increase the quantity and quality of content, improve overall analysis, and disseminate access to both raw and annotated data. Dissemination of information through our web portal includes direct access to resources such as documentation, public datasets, reference atlases, and recordings of workshops and tutorials.

The intellectual merit of this proposal has allowed for the systematic study of intrinsic and extrinsic structural features of synapses. We have accomplished a centralized hub to disseminate images, enhanced tools, and analysis methods to discern the variation in synapse structure across different cell types, brain regions and species, as well as determine the subcellular resources scale with synapse strength as reflected in number and size. In addition, we are able to share our findings with the broader neuroscience community at a global level.

Lastly, the broader impacts from this award have allowed us to provide a centralized hub to the neuroscience community where teachers, students, and fellows are able to retrieve resources, images, analysis tools, and tutorials on the ultrastructure of the brain, as well as the use of computing environments. Through this award, we have reached multiple unrepresented diverse populations and provided travel grants to attend in-person workshops and learn from experts in the computational neuroscience discipline. All these resources are still available at no charge to the community.


Last Modified: 12/20/2024
Modified by: Kristen Harris

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