| NSF Org: |
DUE Division Of Undergraduate Education |
| Recipient: |
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| Initial Amendment Date: | August 7, 2017 |
| Latest Amendment Date: | August 7, 2017 |
| Award Number: | 1734821 |
| Award Instrument: | Standard Grant |
| Program Manager: |
Ellen Carpenter
DUE Division Of Undergraduate Education EDU Directorate for STEM Education |
| Start Date: | September 1, 2017 |
| End Date: | August 31, 2019 (Estimated) |
| Total Intended Award Amount: | $237,499.00 |
| Total Awarded Amount to Date: | $237,499.00 |
| Funds Obligated to Date: |
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| History of Investigator: |
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| Recipient Sponsored Research Office: |
360 HUNTINGTON AVE BOSTON MA US 02115-5005 (617)373-5600 |
| Sponsor Congressional District: |
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| Primary Place of Performance: |
177 Huntington Avenue Boston MA US 02215-5005 |
| Primary Place of
Performance Congressional District: |
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| Unique Entity Identifier (UEI): |
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| Parent UEI: |
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| NSF Program(s): |
ECR-EDU Core Research, IntgStrat Undst Neurl&Cogn Sys |
| Primary Program Source: |
04001718DB NSF Education & Human Resource |
| Program Reference Code(s): |
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| Program Element Code(s): |
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| Award Agency Code: | 4900 |
| Fund Agency Code: | 4900 |
| Assistance Listing Number(s): | 47.076 |
ABSTRACT
How does the brain compute? Understanding this process could lead to many advances in science and technology. The Boyden, Flavell, Barabasi, and Tegmark groups propose to examine how the cells within the brain of a simple animal work together to generate the computations that underlie behavior. The teams will study C. elegans, a small worm with just a few hundred neurons, yet capable of learning and adaptive behavior in complex real-world environments. The teams will apply new technologies to measure and control the neural circuits of C. elegans, in order to investigate how they works. The project will also generate new mathematical tools to analyze the data that is collected - tools that could help analyze how the brain goes wrong in disorders such as Parkinson's or Alzheimer's. Using the data acquired, the project will reveal how brain circuits compute, which could inspire new algorithms for machine learning and computer information processing. These in turn could have broad impact on economic prosperity as well as in advancing human quality of life.
The Boyden, Flavell, Barabasi, and Tegmark groups will launch a novel integrative endeavor to reveal how entire nervous systems - from sensory input neurons, to motor output neurons, and including the networks that underlie learning, decision making, and other processes - work together as emergent wholes to generate the computations that underlie behavior. They will utilize C. elegans, with just 302 neurons, yet capable of learning and adaptive behavior in complex real-world environments. They will optimize and deploy novel technologies, including a new fluorescent voltage indicator for C. elegans, and a method for 3-D visualization of entire nervous systems with molecular information via physical expansion by up to 10,000 fold in volume. They will record neural and behavioral dynamics, imaging the activity of neurons throughout entire brains and even entire nervous systems of freely moving as well as fictively behaving C. elegans engaged in complex decision-making tasks, or forming new memories. They will then use expansion microscopy to map the structure and molecular profiles of entire individual nervous systems. They will analyze the resultant network structures to determine how individual variation in these features connect to details of an individual's behavior, and make mathematical models of the relevant neural circuits capable of predicting how the nervous system would respond in complex contexts. The outcome of their work will yield radical new theories of how nervous systems operate, as well as a diversity of tools for the neuroscience and computational communities.
This project is funded by Integrative Strategies for Understanding Neural and Cognitive Systems (NSF-NCS), a multidisciplinary program jointly supported by the Directorates for Computer and Information Science and Engineering (CISE), Education and Human Resources (EHR), Engineering (ENG), and Social, Behavioral, and Economic Sciences (SBE).
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 Boyden, Flavell, Barabasi, and Tegmark labs set out to develop a toolbox that could enable entire C. elegans nervous systems to be analyzed, and to apply these tools to the understanding of how neurons work together in networks to implement complex, emergent behaviors. C. elegans is an appealing species to study, because it has only 302 neurons, and the connectivity is known.
The Boyden lab applied a powerful inventions of theirs, expansion microscopy, to C. elegans. In expansion microscopy, a swellable polymer is synthesized throughout a biological specimen, the specimen is chemically softened, and then adding water makes the specimen bigger. The net result is that specimens can be imaged with nanoscale precision on ordinary microscopes. The Boyden lab applied C. elegans-optimized expansion microscopy for the analysis of gene expression patterns, and synaptic proteins, in C. elegans. The Boyden lab also implemented fast microscopes and microfluidics to enable worms to be imaged while behaving, and also adapted reagents for live neural imaging, such as novel calcium and voltage indicators, to the worm context.
The Boyden and Tegmark groups, working together, developed algorithms for the automated alignment of neural activity data collected from behaving worms, to anatomy atlases. This innovation provides a key link between neural dynamics data and neural anatomy data from worms.
The Flavell lab analyzed neural dynamics in C. elegans, in the context of behavior, and completed important advances in the study of neural circuits. Particularly, they made technological advances in the approaches that can be used to monitor the activity of large populations of brain cells in freely-behaving animals. These advances are both related to fluorescent sensors of neural activity and new software to analyze complex brain imaging data. They used these tools to examine how individual animals switch between brain states during behavior. Their findings establish mechanisms in the brain that underlie state switches in behavior, and have begun to define how learning alters large-scale brain networks.
The Barabasi lab applied network theory methods to analyze C. elegans data. In particular, network controllability was demonstrated to be able to discern fundamental features of locomotion in C. elegans, specifically the involvement of individual and groups of neurons. Surprisingly small sets of predicted neurons and affected muscles were recovered, some of which have been experimentally tested, and the rest of which provide future experimental hypotheses for the community. These results are highly robust to variations in the wiring diagram, and can be recovered with recently updated data.
In summary, these four groups, working together, have pioneered a new way to integratively look at neural circuits, and to apply such tools to examine how neural networks operate in the worm C. elegans. The results may have implications for many fields, such as artificial intelligence, computer science, and control theory, in addition to furthering our fundamental knowledge about the brain.
Last Modified: 03/02/2020
Modified by: Albert-Laszlo Barabasi
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