By combining two whole-brain scale datasets with multi-millions of cells profiled by single-cell RNA-sequencing or the spatial transcriptomic method, MERFISH, we have created a comprehensive and high-resolution transcriptomic and spatial cell type atlas for the whole adult mouse brain. The atlas identified over 5,300 potential cell types, revealing astonishing cell type diversity across the brain, a high degree of correspondence between transcriptomic identity and spatial specificity for each cell type, and unique characteristics of cell type organization in different brain regions. The study also reveals highly diverse expression patterns of various neurotransmitters and neuropeptides in different cell types, and that transcription factors are major determinants of cell type classification in the adult brain. This project is supported by the BRAIN Initiative Cell Census Network (BICCN) with funding from NIH/NIMH.

Allen Brain Cell (ABC) Atlas

The developing mouse brain is a foundational experimental model for investigation of the origins of cell types in the mammalian brain. We are generating a comprehensive, spatially and temporally resolved, cellular-resolution atlas of the whole developing mouse brain, spanning the entire period of embryonic and postnatal brain development, using single-cell and spatial transcriptomic and multiomic technologies. This work will enable a deep understanding of the mechanisms of mammalian brain development and neurodevelopmental disorders. This project is supported by the BRAIN Initiative Cell Atlas Network (BICAN) with funding from NIH/NIMH.

BICAN: A cell census of the developing human brain

Drugs of abuse devastate the life of millions of people, yet how these drugs (such as cocaine and opioids) affect the brain remains poorly understood. Utilizing the massive amount of cell-type information we have accumulated, we are conducting a systematic investigation of brain-wide, single-cell level gene expression changes induced by acute or chronic use of cocaine or opioids in mice. This work will lead to the identification of specific cell types and gene targets, as well as generalizable mechanisms, that mediate the addictive effects of these drugs, and facilitate the development of better treatments for drug abuse and addiction. This project is supported by funding from NIH/NIDA.

Brain cell types form functionally specific circuits via synaptic and extra-synaptic connections. To unravel the brain-wide circuit networks and create a mesoscale connectome, we have been mapping the input and output connections of specific cell types in the mouse brain using recombinant adeno–associated virus (AAV) mediated anterograde tracing and recombinant rabies virus mediated retrograde trans-synaptic tracing, combined with cell-type targeting genetic tools. A current focus is on understanding the cortex-basal ganglia-thalamus network that mediates brain functions such as movement, reward and cognition. This project is partly supported by the BRAIN Initiative Cell Census Network (BICCN) with funding from NIH/NIMH.

Allen Mouse Brain Connectivity Atlas

Transgene mouse line characterization

Neural circuits, the physical substrates that enable conscious thoughts and complex behaviors, are composed of myriad interconnected neurons. Unraveling the connections of different types of neurons thus provides a foundation for understanding brain structures and functions. However, tracing thin individual axons with nanometer-scale diameters, which are also tightly packed with many other axons, across centimeters of brain matter is very labor intensive and error-prone. To overcome these challenges, we develop RNA barcoding and in situ sequencing-based techniques to map neuronal types and connections with unprecedented throughput and resolution. By making circuit mapping expotentially faster, cheaper, and more accurate, we aim to understand brain-wide organization of cell type connectivity, their development, and their evolution.

Barcoded Connectomics team