The main interest of the Kim lab is to understand structural and functional organization of the mammalian brain using mice as an animal model. Particularly, we are interested in understanding neural circuit basis of behavior (with emphasis in social behavior) while examining their cellular components (e.g., neurons and vasculature) in the whole brain. We have overall three different developmental time points of investigation.
Early postnatal development is critical to establish local and global neural circuit based on activity dependent synaptic plasticity. We are examining how neural circuit develops in this sensitive period of time and how such process is altered in neurodevelopmental disorders (e.g., autism).
Social behavior is complex, requiring the integration of multiple sensory modalities, internal state information, and memories of prior experience in order to generate highly nuanced responses to diverse environmental scenarios. We utilize various system neuroscience tools (e.g., fiberphotometry and virus based circuit manipulation) to understand how different neural circuit components regulate social behavior.
Structural and functional changes in neurovasculature are highly implicated in normal aging and many neurodegenerative disorders (e.g., Alzheimer's disease). We are establishing highly detailed map of neurovasculature in the whole mouse brain to understand its changes with different biological and pathological variables.
We use an automated 3D microscopy system, called "Serial Two-photon tomography", to image whole mouse brain with cellular resolution. We use this imaging method with a sophisticated data processing pipeline to systematically analyze target signals in the entire mouse brain. Previously, we used this method to perform cFos based activity mapping (Kim et al., 2015, Cell Reports), quantitative cell type mapping (Kim et al., 2017, Cell), and brain-wide axonal projection mapping (Jeong and Kim et al., 2016 Scientific Reports).
Anatomical atlas in standard coordinates plays a central role to integrate and interpret findings from different studies. Recently, Allen Brain Institute released the adult mouse brain common coordinate framework (CCF) with seamless 3D high resolution images. Yet, majority of the past and on-going research relies on another atlas, created by Franklin and Paxinos (FP). Allen and FP anatomical labels often use different boundaries and nomenclatures of similar brain regions, creating confusion in interpreting anatomical regions. Furthermore, areas such as dorsal striatum remain unsegmented in both labels due to lack of distinct cytoarchitecture features. To overcome the issues, we created FP based labels into the Allen CCF, creating two independent labels merged into a single atlas framework. We used cell type specific transgenic mice and a MRI atlas to adjust and validate our labels. Moreover, we added detailed segmentation in dorsal striatum based on topographical cortico-striatal projectome data. Lastly, we digitized our anatomical labels to be used a bioinformatics tool and provide comprehensive comparison between Allen and FP labels. Our new label in the CCF is freely available via our website, providing valuable resource to isolate and identify brain anatomical structures.Atlas Project Link
Oxytocin receptor (OTR) plays critical roles in the development and expression of social behavior. Previous studies suggested that OTR expression is developmentally regulated with peak cortical expression in early postnatal period. However, quantitative understanding of OTR expression changes across different brain regions remains largely unknown. Thus, we examined the expression patterns of OTR positive cells throughout the whole brain at postnatal (P) periods (P7, 10, 14, 18, 21, 28) and in adulthood (P56) using transgenic reporter mice (OTR-eGFP). We used serial two-photon tomography to image the entire brain at cellular resolution and quantified fluorescently labeled cells with newly generated 3D postnatal brain templates at P7, 14, 21, and 28. We found significant heterogeneity in temporal pattern of OTR expression in brain regions including cortex. We then identified that transient OTR expression is mainly driven by OTR downregulation, not by cell death, using OTR-Cre:Ai14 for cumulative labeling. Lastly, we found significant delay of cortical OTR peak at P21 in OTR heterozygote mice (OTRvenus/+). We created a website to share the high-resolution imaging data as community resource for further data mining. In summary, our result provides essential quantitative data to understand postnatal OTR expression in the mouse brain.
An intricate web of blood vessels in the mammalian brain provides essential oxygen and nutrients to power the energy demands of the brain. The structure of the brain’s microvasculature provides the extraordinary surface needed for a high level of energy exchange and clearance of metabolic wastes. Small vessel pathologies are involved in cognitive decline associated with aging and many brain disorders. Mounting evidence supports the idea that neuronal activity dynamically regulates diameter of small vessels to maintain energy homeostasis. Moreover, emerging evidence suggests that 3D distribution and function of small vessels, and their interaction with vasomotor neurons are heterogeneous in different brain regions. Interestingly, some brain regions are more susceptible than others to age related degeneration, which can be linked to many neurological conditions with brain region specific symptoms such as Alzheimer's disease. To understand the underlying neurovascular mechanisms affected in health and pathological conditions, we create a precise 3D map of micro vessels and cell types controlling vessel motility in the entire mammalian brain using the mouse as a model. Furthermore, we examine neurovascular changes during aging. This work will establish reference maps that are needed as a foundation for the further study of neurovascular architectures supporting normal cognitive function and their changes in various neuropathologies.