Funded Awards

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Investigator
Osten, Pavel
Institute
Cold Spring Harbor Laboratory
Year Funded
2017
FOA Number
Status
Active
Project Number
Priority Area
  • Cell Type
  • Circuit Diagrams
Summary
Although neuronal properties have been studied for over a century, we still have an incomplete idea of how different cell types are distributed throughout the brain. Osten and colleagues will use the automated Cell Counting and Distribution Mapping (CCDM) pipeline that they developed to express specific neuronal markers in the brains of adult mice, take high-resolution images of the neurons, and then spatially map their location. They plan to identify the distribution patterns and somato-dendritic morphology of more than 80 molecularly defined cell types. These data will provide detailed anatomical information about cell circuits that can then be integrated with molecular data to better define cell types in the brain.
Investigator
Dougherty, Darin D (contact) Widge, Alik S
Institute
Massachusetts General Hospital
Year Funded
2018
FOA Number
Status
Active
Project Number
Priority Area
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity
Summary

4-7 million Americans suffer from obsessive-compulsive disorder (OCD), and at least half of these patients do not receive adequate relief from medication or talk therapy. Deep brain stimulation (DBS) is used as a treatment for patients with intractable OCD, but only works for about half of these patients. In an effort to improve DBS for OCD, Dougherty and Eskandar have proposed to develop and test in a small early feasibility study a next-generation, brain circuit-oriented DBS treatment for drug-refractory OCD. In their project, they will measure brain activity to test a hypothesis about the specific circuit dysfunction that underlies OCD, and they will test whether DBS stimulation can disrupt this circuit dysfunction in order to relieve OCD symptoms.

Investigator
Dougherty, Darin D (contact) Eskandar, Emad N
Institute
Massachusetts General Hospital
Year Funded
2016
FOA Number
Status
Active
Project Number
Priority Area
  • Human Neuroscience
  • Interventional Tools
  • Monitor Neural Activity
Summary
4-7 million Americans suffer from obsessive-compulsive disorder (OCD), and at least half of these patients do not receive adequate relief from medication or talk therapy. Deep brain stimulation (DBS) is used as a treatment for patients with intractable OCD, but only works for about half of these patients. In an effort to improve DBS for OCD, Dougherty and Eskandar have proposed to develop and test in a small early feasibility study a next-generation, brain circuit-oriented DBS treatment for drug-refractory OCD. In their project, they will measure brain activity to test a hypothesis about the specific circuit dysfunction that underlies OCD, and they will test whether DBS stimulation can disrupt this circuit dysfunction in order to relieve OCD symptoms.
Investigator
Bejerano, Gill Lois, Carlos Mitra, Partha Pratim Nelson, Sacha B (contact)
Institute
Brandeis University
Year Funded
2014
FOA Number
Status
Complete
Project Number
Priority Area
  • Cell Type
Summary
To gain a deeper understanding of how cells have evolved specialized features, Dr. Nelson and colleagues will create transgenic strains of rats and mice that carry identical genetic modifications in many different cell types and see how the properties of these cells diverge across species.
Investigator
Pehlevan, Cengiz Samuel, Aravinthan D. Sternberg, Paul Warren (contact) Zhen, Mei
Institute
California Institute Of Technology
Year Funded
2019
FOA Number
Status
Active
Project Number
Priority Area
  • Integrated Approaches
Summary

Past experiences often drive how an animal develops. How does the brain draw on those experiences to guide developmental choices? Dr. Sternberg’s team will take a detailed look at the C. elegans decision-making circuit during development, using state-of-the-art molecular tools, computational modeling, and functional imaging, to examine how sensory inputs influence the developmental choices an animal makes. With the help of advanced technology, Dr. Sternberg’s colleagues will see how brain circuits change before, during, and after decision making.

Investigator
Regev, Aviv Sanes, Joshua R (contact) Schier, Alexander F Zhang, Yi
Institute
Harvard University
Year Funded
2014
FOA Number
Status
Complete
Project Number
Priority Area
  • Cell Type
Summary
Dr. Sanes and colleagues will use new methods of genetic screening to comprehensively catalog and distinguish different kinds of cells across species and brain regions.
Investigator
Waller, Laura
Institute
University Of California Berkeley
Year Funded
2016
FOA Number
Status
Complete
Project Number
Priority Area
  • Monitor Neural Activity
  • Interventional Tools
Summary
State-of-the-art techniques for measuring neural activity on a large scale still lack the ability to measure signals from across many brain regions at high speed and with cellular resolution. Borrowing from recent advances in 3D photography, Waller and her colleagues will develop an optical imaging system that will not only capture the intensity of light emitted from active, fluorescing neurons, but it will also capture the angle of the emitted light. Combining light intensity and angle allows for reconstruction of neural activity in 3D. This system, which will be relatively inexpensive and easy to set up, has the potential to record from millions of individual neurons at speeds faster than conventional imaging methods.
Investigator
Eden, Uri Tzvi Frank, Loren M Ganguli, Surya Kepecs, Adam (contact) Kramer, Mark Alan Machens, Christian Tolosa, Vanessa
Institute
Cold Spring Harbor Laboratory
Year Funded
2015
FOA Number
Status
Complete
Project Number
Priority Area
  • Cell Type
  • Circuit Diagrams
  • Integrated Approaches
  • Interventional Tools
  • Monitor Neural Activity
  • Theory & Data Analysis Tools
Summary
Dr. Kepecs and colleagues are investigating how information is integrated into decision making, and then further transformed into behavior. This project focuses on understanding information flow across specific regions of the brain in trained rats. By performing parallel, large-scale, simultaneous electrical recordings of neural activity in these different brain regions while the animals perform two different types of decision-making tasks, these researchers hope to observe how activity in one area influences activity in a downstream area. In addition, there are plans to identify and manipulate the activity of neurons that connect these brain areas to understand the causal relationships governing information flow among these regions. Gaining such mechanistic insights into how the brain processes information will provide insights into how both the normal and disordered brain operates.
Investigator
Shadlen, Michael Neil
Institute
Columbia University Health Sciences
Year Funded
2019
FOA Number
Status
Active
Project Number
Priority Area
  • Integrated Approaches
Summary

Many cognitive functions rely on brain mechanisms involved in decision-making. Dr. Shadlen and colleagues aim to better understand how the brain makes increasingly complex decisions by using visual processing as a model. By combining complex behavioral tasks and multichannel neural recordings from multiple brain regions in nonhuman primates, the team will explore context-dependent interactions between brain regions; changes that occur during decision-making; and the timing at which an organism must make two distinct decisions about a single object.

Investigator
Costa, Rui M. (contact) Jessell, Thomas M.
Institute
Columbia University Health Sciences
Year Funded
2017
FOA Number
Status
Active
Project Number
Priority Area
  • Integrated Approaches
Summary
The mechanisms by which the nervous system produces controlled movements involve interactions between cortical and subcortical regions in the brain, the spinal cord, and muscle, but a clear understanding of these interactions remains elusive. Rui Costa, Thomas Jessell, and colleagues are planning to study the functional and computational logic of connectivity between these motor centers to characterize the role of specific corticospinal neurons during movements. When investigating motor control through cell-type-specific connectivity from brain to spinal cord, the team will use optogenetic manipulations and computational modeling to obtain a clear understanding of these circuit mechanisms. This project – in addition to the use of innovative methods – will also provide an understanding of how these systems are preserved across rodent and nonhuman primate species.
Investigator
Buffalo, Elizabeth A
Institute
University Of Washington
Year Funded
2018
FOA Number
Status
Active
Project Number
Priority Area
  • Integrated Approaches
Summary

The circuit mechanisms underlying memory consolidation allow for detailed memory formation. Impairments in these circuits negatively impact patients dramatically with myriad neurological disorders. Dr. Buffalo’s project will study the neural circuits underlying rapid learning, using single-unit and field recordings in human and nonhuman primates (NHP) during the execution of learning- dependent tasks. Alongside electrophysiological recordings in both species during naturalistic and learning task performance and during sleep, the group will perform neural network modeling and state- space analyses. The project could reveal how abstract sensorimotor representations in this circuitry enable “learning to learn” new associations to form memories in humans and NHP.

Investigator
Dougherty, Darin D Widge, Alik S (contact)
Institute
Massachusetts General Hospital
Year Funded
2016
FOA Number
Status
Complete
Project Number
Priority Area
  • Monitor Neural Activity
  • Interventional Tools
  • Theory & Data Analysis Tools
Summary
Deep brain stimulation (DBS) targeting the ventral internal capsule/ventral striatum (VC/VS) is being used as a treatment for those with obsessive compulsive disorder (OCD), but with inconsistent clinical results. As a tool to examine mechanisms underlying this process, Dr. Widge and colleagues will adapt the recently developed "StimVision" software suite to model DBS electrical fields that activate brain tissue, in collaboration with the McIntyre lab (Case Western Reserve University). Using data from their DBS patient cohort, the team will integrate novel algorithms to improve modeling of neural mechanisms underlying the effects of DBS. This research, using StimVision with a specific DBS patient group, will improve understanding of cortical circuits underlying the behavioral effects of DBS, potentially enhancing circuit-oriented therapies.
Investigator
Wang, Yi Xu, Chris (contact)
Institute
Cornell University
Year Funded
2016
FOA Number
Status
Complete
Project Number
Priority Area
  • Monitor Neural Activity
  • Interventional Tools
Summary
One of the major goals of the BRAIN Initiative is mapping neuronal function at multiple spatial scales, from synapses to the whole brain. The proposed project from Xu and Wang will deliver such maps by combining two powerful brain imaging technologies—MRI and multiphoton imaging, a deep-brain, high-resolution imaging technique that Xu has developed with the help of two previous BRAIN awards. The combined imaging device will allow studies of the relationship between neural activity at the cellular and network level.
Investigator
Payne, Christine K
Institute
Georgia Institute Of Technology
Year Funded
2015
FOA Number
Status
Complete
Project Number
Priority Area
  • Monitor Neural Activity
  • Interventional Tools
Summary
Microelectrodes are used to record and stimulate neuronal activity in experimental animals and in human therapeutic applications. However, the injury to tissue when they are implanted, and their mechanical mismatch with brain tissue after implantation, can trigger the brain's immune response, causing them to be encapsulated by glia and other cells and preventing current flow between neurons and the electrical contacts. Payne and her colleagues will use the latest in nanotechnology to develop ultra-thin, flexible nanowires made from a biocompatible polymer which, because of their small size and flexibility, may avoid the immune responses triggered by larger electrodes. The nanowires will be inserted into the brain with micro-capillary tubes and will connect individual neurons to external recording and/or stimulating devices. The nanowires can also be coated with specific molecules that will promote attachment to specific neuron types, allowing for precisely targeted recording or stimulation experiments.
Investigator
Basser, Peter J. Huang, Susie Yi Rosen, Bruce R (contact) Wald, Lawrence L Witzel, Thomas
Institute
Massachusetts General Hospital
Year Funded
2018
FOA Number
Status
Active
Project Number
Priority Area
  • Human Neuroscience
  • Integrated Approaches
  • Interventional Tools
  • Monitor Neural Activity
Summary

Understanding the structural basis of brain function requires spanning multiple spatial scales, from synaptic circuits to whole-brain systems, but current technology is limited in its ability to successfully integrate across these scales. Dr. Bruce Rosen and a team of investigators propose the development of a human magnetic resonance imaging (MRI) scanner that images brain structural connectivity in-vivo. Building upon previous work from the Human Connectome Project (HCP), these tools will advance brain imaging with the capability of estimating cellular and axon level microstructural brain circuits at very high resolution. The project will have the potential to significantly expand our knowledge on hierarchical anatomy and functionality of both healthy and diseased human brains, with impact on both neuroscience research and clinical applications.

Investigator
Collinger, Jennifer
Institute
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
Year Funded
2018
FOA Number
Status
Active
Project Number
Priority Area
  • Human Neuroscience
  • Integrated Approaches
  • Interventional Tools
  • Monitor Neural Activity
Summary

When you reach for a beverage, the way you pick up the drink depends on whether it is in a sturdy mug or a delicate champagne flute, as well as your reach configuration. Dr. Collinger and her colleagues plan to investigate the way environmental context affects motor cortex activity as the brain plans movements, such as grasping an object. Two individuals with tetraplegia will receive implants in their motor cortex to record activity while they use brain signals to control a robotic prothesis in a variety of tasks including grasping an object or grasping into empty space, picking up objects of various sizes and materials, and picking up objects for different goals. A better understanding of how the brain prepares these movements may lead to improved devices and therapies for those with sensory or motor problems. 

Investigator
Gibson, Emily Restrepo, Diego (contact)
Institute
University Of Colorado Denver
Year Funded
2017
FOA Number
Status
Active
Project Number
Priority Area
  • Monitor Neural Activity
  • Interventional Tools
Summary
Optical imaging techniques offer several advantages to understanding neural circuits, including the ability to interrogate a large number of neurons and genetically label specific neuronal subtypes. Diego Restrepo, Emily Gibson, and colleagues will optimize their prototype of a light-weight, two-photon, fiber-coupled, miniature confocal microscope that uses electrowetting lens technology. The new tool will be able to image and stimulate select fluorescently-labeled neurons in a 3D volume in awake-behaving animals. The device can be attached to existing commercial laser scanning microscopes – greatly expanding the number of labs who will be able to benefit from this cutting-edge technology.
Investigator
Sabatini, Bernardo
Institute
HARVARD MEDICAL SCHOOL
Year Funded
2018
FOA Number
Status
Active
Project Number
Priority Area
  • Interventional Tools
Summary

Optogenetics has dramatically advanced neuroscience, allowing the manipulation and monitoring of activity in genetically-defined neurons in the brain using light. However, while deeper brain structures can be accessed using optical fibers, standard fibers only illuminate tissue near their tip and are invasive in small animals. The team will develop light-delivery tools—tapered fiber optics—that allow precise, flexible control of spatially separated groups of neurons. Coupling these optical devices with electrical stimulators, the group plans to interrogate the same neurons using both methods simultaneously and incorporate novel viral preparations to enable genetic change in the neurons through the device. This toolset should expand our ability to manipulate and record neuronal circuits in a less invasive manner.

Investigator
Vaziri, Alipasha
Institute
Rockefeller University
Year Funded
2017
FOA Number
Status
Active
Project Number
Priority Area
  • Monitor Neural Activity
  • Interventional Tools
Summary
Understanding how brain-wide neural network activity underlies behavior is a central goal of neuroscience, and essential to understanding neurological and psychiatric disorders. Vaziri’s group recently innovated microscopy platforms that extend the obtainable spatiotemporal resolution and volume size using calcium imaging. Here, they propose to develop, apply, and disseminate a hybrid system that enables calcium imaging of ~2 million neurons within and across layers of cortex in awake behaving rodents and marmosets. Such a system would capture functional organization and activity patterns of neuronal population dynamics. This project could enable new mechanistic insights into the computational principles of neural information processing.
Investigator
Sur, Mriganka
Institute
Massachusetts Institute Of Technology
Year Funded
2014
FOA Number
Status
Complete
Project Number
Priority Area
  • Cell Type
  • Circuit Diagrams
  • Integrated Approaches
  • Interventional Tools
  • Monitor Neural Activity
  • Theory & Data Analysis Tools
Summary
Dr. Sur and his team will combine a number of cutting-edge, large-scale imaging and computational techniques to determine the exact brain circuits involved in generating short term memories that influence decisions.