| NSF Org: |
DBI Division of Biological Infrastructure |
| Recipient: |
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| Initial Amendment Date: | August 18, 2014 |
| Latest Amendment Date: | August 18, 2014 |
| Award Number: | 1451125 |
| Award Instrument: | Standard Grant |
| Program Manager: |
Robert Fleischmann
DBI Division of Biological Infrastructure BIO Directorate for Biological Sciences |
| Start Date: | September 1, 2014 |
| End Date: | August 31, 2017 (Estimated) |
| Total Intended Award Amount: | $300,000.00 |
| Total Awarded Amount to Date: | $300,000.00 |
| Funds Obligated to Date: |
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| History of Investigator: |
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| Recipient Sponsored Research Office: |
77 MASSACHUSETTS AVE CAMBRIDGE MA US 02139-4301 (617)253-1000 |
| Sponsor Congressional District: |
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| Primary Place of Performance: |
43 Vassar St. Cambridge MA US 02139-4308 |
| 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): |
INSTRUMENTAT & INSTRUMENT DEVP, Cross-BIO Activities |
| Primary Program Source: |
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| 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): | 47.074 |
ABSTRACT
This award is jointly made by two programs: Instrument Development for Biological Research program (IDBR), and Emerging Frontiers (EF), in the Directorate of Biological Sciences (BIO).
Short-term memory is a crucial component of cognitive function and pervades nearly all aspects of our mental lives. Previous research has shown that short-term memory involves multiple cognitive components and diverse brain regions. However, it is not mechanistically understood what regions are involved when, what neuronal subsets are recruited within these regions, or how they interact to represent information relevant to behavior. This proposal aims to elucidate the role of visual, association, and motor cortex in mice performing a visually-cued short-term memory task. This will be accomplished using massive-scale two-photon calcium imaging in behaving mice to measure activity of thousands of neurons simultaneously across these multiple brain regions. Subsequently, optogenetic manipulation of brain regions and of computationally identified neuronal assemblies will be used to determine their causal role in behavior. These technologies and results will have wide impact on understanding neural circuits underlying behavior and cognition. New approaches will be introduced for massive-scale mapping of single neuron activity in relation to a quantifiable behavior. New ways to determine circuit connectivity, and novel combination computational and optogenetic technologies to manipulate critical circuit components, will be introduced. These large data sets will be made widely and freely available, enabling other research groups to avail of these data for novel analyses.
The goal of this proposal is to develop novel tools and provide unprecedented information on neuronal activity patterns and circuits in order to understand the role of multiple cortical areas during short-term memory in mice. Classical electrophysiological recordings are limited to relatively small numbers of neurons with unknown identity. In addition, while microstimulation or pharmacological manipulations can be used to activate or inhibit all the neurons within a local area, it is not possible to selectively excite or inhibit specific neuronal subpopulations that are known to play a role in the behavior. The proposal addresses these issues by developing novel tools to study mice performing a visually-cued memory-guided discrimination task. First, methods for massive scale imaging (up to ten thousand neurons simultaneously) of multiple cortical regions spanning several millimeters in the mouse cortex will be developed. Second, mice will be trained on a visually cued short-term memory task with suitable behavioral richness, including separate sensory, memory and response epochs, so that activity in distributed cortical regions (such as visual, parietal, and frontal motor cortices) can be imaged and the role of individual areas in each epoch can be ascertained. Third, targeted inactivation of specific brain areas will be performed to determine their role in the behavior. Finally, computationally identified neuronal subsets in specific areas will be stimulated in order to determine if they are sufficient for altering behavior. Together, these will be the first studies in the field to link behavior, extremely large-scale multiple-area recordings, and causal manipulations of areas and identified neuronal assemblies. By introducing tools for a radically different approach from previous analyses of memory and memory-guided functions, it is expected that the project will have a significant impact on the field.
PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH
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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.
Project Outcomes Report
One of the fundamental functions of the central nervous system is to gather input through the senses from the environment and convert them into a directed action such as walking around an obstacle or picking up an object. This relatively simple seeming activity requires diverse areas of the brain to communicate information in a precise manner to result in a decision and action. To study the flow of information that leads to a decision, the activity of large populations of neurons from distinct regions are recorded, decoded and their activity matched to behavioral actions. Our project has utilized rodents trained on a two-alternative choice task, in which the animal reports the location of a visual cue by rotating a ball in the same direction. Utilizing receptors that in response to light activate or deactivate neuronal activity, we are able to decipher the direction of information flow in the brain, and the content of the information conveyed into and by each brain region. This is the first step in understanding how the brain takes relevant information from the environment, processes it, and comes to a decision regarding any necessary action.
Broadly, our research provides an understanding of the link between the activity of distinct populations of neurons and a behavioral outcome. We have pioneered new approaches to the mapping of neuronal activity in response to a measurable behavior. We have introduced new methods in mapping connections in the brain, using computer modeling and optical manipulation of neuronal populations. Our data will be made available to the public, allowing other groups to generate novel computer models of how the brain processes information, as well as data sets for educational and training purposes such as open online course in neuroscience such as those provided through MIT’s edX platform.
Last Modified: 12/07/2017
Modified by: Mriganka Sur
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