The overarching goal of neuroanatomy is to establish a structural framework to integrate multiscale and multi-modalinformationandtoprovidearoadmapthatguidestheexplorationofneuraldynamicsandbrain function. ?Anatomic? neuron types can be described by their location, morphology, and connectivity. As morphologyisoneofthemostintuitivedepictionsofcelltypesthatreflectstheirinput-outputconnectivity,the visualization, characterization and quantification of their complete and detailed shapes are key to the identification and classification of anatomic neuron types. However, these have remained enduring challengesforoveracentury,asmostvertebrateneuronsaresimultaneouslysmallandlarge,spanningvast spatialscalesfromsubmicrontocentimeter(e.g.corticospinalneuronsconnectingcortextospinalcord).The overallgoalsoftheAnatomySegmentareto:1)establishaForebrainProjectionCellAtlasthatintegrates in-depthmulti-modalityanatomicandmolecularinformationacrosscerebralcortex,basalganglia,thalamus, and hypothalamus. A forebrain projection neuron atlas will provide a core skeleton that anchors nearly all other brain structures and the transcriptome cell atlas constructed in the Molecular Segment;? 2) advance current and emerging imaging technologies and pipelines with improved resolution, throughput and lower cost. We will use several state-of-the-art imaging technologies and pipelines to obtain multi-modal, high- resolution whole brain datasets on cell location, morphology, projection, and connectivity of vast sets of forebrain neurons, all registered in the mouse brain Common Coordinate Framework (CCF). To achieve high-resolution brain-wide imaging, we will use 1) Serial Two-Photon tomography (STP) to image marker- defined neuronal body distribution, 2) STP to image axon projection patterns of genetic and virally-labeled neuron subpopulations, 3) fluorescence Micro-Optical Sectioning Tomography (fMOST) to image and reconstruct the complete morphology of single neurons ? the ultimate resolution for anatomic cell typing. Importantly, this anatomical forebrain atlas will integrate single-cell molecular information collected and positionally mapped for the same cell types in the Molecular Segment, towards a close-to-completion MolecularandAnatomicalatlasofthemouseforebrain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19MH114821-04
Application #
9937836
Study Section
Special Emphasis Panel (ZMH1)
Project Start
Project End
Budget Start
2020-06-01
Budget End
2021-05-31
Support Year
4
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Cold Spring Harbor Laboratory
Department
Type
DUNS #
065968786
City
Cold Spring Harbor
State
NY
Country
United States
Zip Code
11724
He, Miao; Huang, Z Josh (2018) Genetic approaches to access cell types in mammalian nervous systems. Curr Opin Neurobiol 50:109-118