cell transcriptomics

Rejuvenating the Alzheimer’s brain: Challenges & Opportunities

Dorothy J Killam Lecture: Cell Type Classification and Circuit Mapping in the Mouse Brain

To understand the function of the brain and how its dysfunction leads to brain diseases, it is essential to have a deep understanding of the cell type composition of the brain, how the cell types are connected with each other and what their roles are in circuit function. At the Allen Institute, we have built multiple platforms, including single-cell transcriptomics, single and multi-patching electrophysiology, 3D reconstruction of neuronal morphology, high throughput brain-wide connectivity mapping, and large-scale neuronal activity imaging, to characterize the transcriptomic, physiological, morphological, and connectional properties of different types of neurons in a standardized way, towards a taxonomy of cell types and a description of their wiring diagram for the mouse brain, with a focus on the visual cortico-thalamic system. Building such knowledge base lays the foundation towards the understanding of the computational mechanisms of brain circuit function.

Neurobiology of Social Behavior

Social interactions are central to the human experience, yet it is also one of the faculty of the brain that is the most impaired by mental illness. Similarly, social interactions are essential for animals to survive, reproduce, and raise their young. Over the years, my lab has attempted to decipher the unique characteristics of social recognition: what are the unique cues that trigger distinct social behaviors, what is the nature and identity of social behavior circuits, how is the function of these circuits different in males and females and how are they modulated by the animal physiological status? In this lecture, I will describe our recent progress in using genetic, imaging, molecular and behavioral approaches to understand how the brain controls specific social behaviors in both males and females, and how areas throughout the brain participate in the positive and negative controls of specific social interactions. I will also describe how new approaches of single cell transcriptomics have enabled us to uncover specific cell populations involved in distinct social behaviors and the basis of their activity modulation according to the animal state.

Toward a Comprehensive Classification of Mouse Retinal Ganglion Cells: Morphology, Function, Gene Expression, and Central Projections

I will introduce a web portal for the retinal neuroscience community to explore the catalog of mouse retinal ganglion cell (RGC) types, including data on light responses, correspondences with morphological types in EyeWire, and gene expression data from single-cell transcriptomics. Our current classification includes 43 types, accounting for 90% of the cells in EyeWire. Many of these cell types have new stories to tell, and I will cover two of them that represent opposite ends of the spectrum of levels of analysis in my lab. First, I will introduce the “Bursty Suppressed-by-Contrast” RGC and show how its intrinsic properties rather than its synaptic inputs differentiate its function from that of a different well-known RGC type. Second, I will present the histogram of cell types that project to the Olivary Pretectal Nucleus, focusing on the recently discovered M6 ipRGC.

Identification of defects of human cortical neuron development using single cell transcriptomics

Impact of PD in Caudate & Putamen using single-cell transcriptomics: special focus on Oligodendrocytes and OPCs