Astrocyte Modulation of Neural Circuit Function and Behavior

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  • U19 – brief description overall project goals, competing circuit theories being developed/studied/integrated: 
    • “What is the function of glial cells in neural centers? The answer is still not known, and it may remain unsolved for many years to come until scientists find direct methods to attack it.” (Ramon y Cajal, 1901). This prophecy turned out to be accurate. Astrocytes, one of the most abundant cell types in the brain, have long been thought of as primarily passive support cells. Over the past two decades, studies indicate that astrocytes play pivotal roles in nervous system development, function, and diseases. However, a major unresolved issue in neuroscience is how astrocytes integrate diverse neuronal signals under healthy conditions, modulate neural circuit structure and function at multiple temporal and spatial scales, and how aberrant excitation and molecular output influences sensorimotor behavior and contributes to disease. The overall goal of this U19 Team-Research BRAIN Circuit Program project is to address this fundamental issue by developing a deeper mechanistic understanding of astrocytes’ roles in neural circuit operation, complex behaviors, and brain computation theories. Two overarching questions will be addressed: 1) How do astrocytes temporally and spatially integrate molecular signals from the diverse types of local and projection neurons activated during sensorimotor behaviors. 2) How do astrocytes convert this information into functional outputs that modulate neural circuit structure and function at different spatial and temporal scales. A multidisciplinary, comprehensive effort is proposed to address these questions that can only be completed through close collaboration between researchers with unique and complementary expertise. An innovative multi-scale approach integrating functional, anatomical, and genetic analyses with theoretical modeling will be leveraged. This approach involves quantitative behavioral assays, large-scale imaging of cellular and molecular dynamics, targeted cell-type-specific manipulations, high- throughput omic techniques, genetic profiling, protein engineering, machine learning, and computational modeling. By integrating experimental and theoretical approaches, molecular, cellular, and circuit mechanisms will be determined through which astrocytes influence neural circuits and contribute to complex behaviors and brain computation theories. The experimental and data analysis tools developed as part of this project will be invaluable for the broader neuroscience community.
  • Description of how Data Science Core is complying to the criteria of the FAIR principles:
    • Data Science Core will build a digital infrastructure in the form of a multi-tier services-oriented architecture. The products of the other Research Projects will be collected via protocols that are with rich matadata and amenable to a digital representation. These will then be unified via spatial registration in a common coordinate system. Data files with the appropriate format will be made available on the public internet. A user-friendly web-based interface will ensure that users can easily navigate between individual data sets and also can visualize relationships between data sets across the domains from the other Research Projects. Besides hosting the data in our own server, we will deposit all the data to the relevant public archive. 
  • List of Data Types in U19:
    • Light Microscopy data: confocal or two-photon calcium, PKA, dopamine, and other neuromodulators imaging; light-sheet imaging of cleared tissues; expansion microscopy imaging; super-resolution fluorescence imaging.
    • Electron microscopy data: Correlative light and EM microscopy imaging.
    • Neurophysiology data: LFP recordings.
    • Omics Data: MInT-ChIP for measuring histone modifications; RNA-seq; ATAC Sequencing; Proteomics.
  • Common Data Elements in U19:
    • All groups will have confocal or two-photon calcium imaging data. 
    • Super-resolution fluorescence imaging and EM microscopy imaging will be used by more than one group.
    • All the analysis will be standardized and coordinated among groups.
  • Data Sharing goals in U19:
    • The first goal is to streamline the data sharing and access within our U19.
    • Then, we will share the data for reuse within the BRAIN initiative communities.
    • Finally, we will contribute data to the general science community national and worldwide.
  • Data science tools being used in project:
    • ImageJ
    • R
    • Matlab
  • Data science tools being developed for project:
  • Data science approaches to be shared with other U19’s:
  • Data science challenges that could benefit from discussion with other U19’s:
    • How the sharing of the test version and the feedback within the U19 community could speed up the tool development and adoption.


Brain PI Meeting materials

2022 Update:

Link to Poster:


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