From Cell Types to Circuits: A Spatiotemporal Map of the Developing Early Postnatal Mouse Brain
Restricted (Penn State Only)
- Author:
- Liwang, Josephine
- Graduate Program:
- Neuroscience
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- February 10, 2025
- Committee Members:
- Yongsoo Kim, Program Head/Chair
Yingwei Mao, Outside Unit Member
Anirban Paul, Major Field Member
Yongsoo Kim, Chair & Dissertation Advisor
Fumiaki Imamura, Outside Field Member - Keywords:
- brain
development
atlas
cell type
microglia
GABAergic
neurodevelopment
growth chart - Abstract:
- Understanding the mechanisms of postnatal brain development is vital for uncovering the complexities of brain function, evolution, and pathology. This dissertation examines postnatal brain development using the mouse as an animal model of research, with an emphasis on neuronal and glial developmental trajectories and region-specific growth patterns. From the primary research conducted, high-resolution 3D atlases of the early postnatal mouse brain (epDevAtlas) were constructed for postnatal days (P) 4, 6, 8, 10, 12, and 14, utilizing Allen CCFv3 anatomical labels and validated with 11 cell type-specific transgenic mouse lines. These atlases quantified regional volumetric growth and cell type distribution, offering insight into typical and pathological development. Region-specific density changes were identified in GABAergic neurons, cortical layer-specific cells, and microglia, underscoring their roles in shaping brain architecture during critical early developmental stages. To map functional circuit maturation, a whole-brain mapping method utilizing a reporter system for the immediate early gene Npas4 was developed, providing the first spatiotemporal map of circuit maturation during this period. Open-access web visualizations and repositories were then created to facilitate community access to the cell-type (https://kimlab.io/brain-map/epDevAtlas) and circuit (https://kimlab.io/brain-map/DevATLAS) developmental data. These findings significantly enhance our understanding of the intricate processes underlying brain development, offering new tools for experimental models and therapeutic strategies. They also contribute to a deeper appreciation of neurodevelopment, laying a foundation for advancing research into brain disorders.