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U01 - Dong 1U01MH114829-01

Anatomical Characterization of Neuronal Cell Types of the Mouse Brain

A comprehensive understanding of neuronal cell type diversity will provide an essential guide to their selective manipulation and illuminate cell type specific contributions to health and disease. Accordingly, the Brain Initiative Cell Census Network (BICCN) is unifying the efforts of laboratories with unique expertise in anatomy, genetics, electrophysiology, and function to classify neurons and ultimately create a common 3D atlas of integrated cell type data.  Toward this end, our project will be collecting and analyzing data to fully characterize the anatomic features of neuronal cell types.  Collectively our experiments will reveal cell type anatomic location, morphology, and comprehensive connectivity, including both their monosynaptic input/output organization.  The major plan is:
 

  • Using mesoscale quadruple retrograde tracing, we will initially characterize cell types based on the anatomical location of their connectional start and end points.
  • Advanced viral tracing tools will subsequently refine specific axonal projections, collaterals, and projection fields of the cell types. Combinatorial tracing methodologies will be applied to also determine the discrete connectional inputs providing a more complete anatomical characterization of the different cell populations.
  • The morphological features will be revealed using rabies tracing in CLARITY-processed tissue. Furthermore, newly constructed viral circuit tracers will be applied in combination with Expansion Microscopy and multiphoton imaging to determine the spatial organization of synaptic inputs from different sources to their corresponding cell types.
  • A web-based visualization platform also will be developed to enable the viewing of raw, analyzed, and visualized cell type anatomy data.

Project Leadership

Hong-Wei Dong, Ph.D.  (Principal investigator)
Professor of Neurology, Director of Center for Integrative Connectomics, 
USC Mark and Mary Stevens Neuroimaging and Informatics Institute
Keck School of Medicine of University of Southern California
http://donglab.loni.usc.edu/

 

Giorgio A. Ascoli, Ph.D (Principal investigator)
Professor of Molecular Neuroscience, Center for Neural Informatics, Structure, and Plasticity, Krasnow Institute for Advanced Study, George Mason University
http://krasnow1.gmu.edu/cn3/ascoli/

 

Byung Kook Lim, Ph.D. (Principal investigator)
Assistant Professor, Division of Biological Sciences, Neurobiology, University of California, San Diego
https://biology.ucsd.edu/research/faculty/byl015

 

Ian Wickersham, Ph.D. (Co-investigator)
Principal Investigator, Genetic Neuroengineering Group
Principal Research Scientist, McGovern Institute for Brain Research
Massachusetts Institute of Technology
https://mcgovern.mit.edu/profile/ian-wickersham/

 

Houri Hintiryan, Ph.D. (Project manager)
Research Assistant Professor, Center for Integrative Connectomics 
USC Mark and Mary Stevens Neuroimaging and Informatics Institute
Keck School of Medicine of University of Southern California
https://loni.usc.edu/about_loni/people#Houri_Hintiryan

Project Data Types

  • Multiple retrograde tracing data
  • Cre-dependent anterograde tracing data
  • Trans-synaptic rabies tracing data
  • Spaghetti monster rabies morphology data
  • G-deleted rabies morphology data
  • CLARITY facilitated morphology data
  • Digitally reconstructed neuron morphology data
  • Expansion Microscopy data
  • Multiphoton and lightsheet microscopy image data
  • Histology

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