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Comprehensive knowledge of the brain's wiring diagram is fundamental for understanding how the nervous system processes information at both local and global scales. However, with the singular exception of the C. elegans microscale connectome, there are no complete connectivity data sets in other species. Here we report a brain-wide, cellular-level, mesoscale connectome for the mouse. The Allen Mouse Brain Connectivity Atlas uses enhanced green fluorescent protein (EGFP)-expressing adeno-associated viral vectors to trace axonal projections from defined regions and cell types, and high-throughput serial two-photon tomography to image the EGFP-labelled axons throughout the brain. This systematic and standardized approach allows spatial registration of individual experiments into a common three dimensional (3D) reference space, resulting in a whole-brain connectivity matrix. A computational model yields insights into connectional strength distribution, symmetry and other network properties. Virtual tractography illustrates 3D topography among interconnected regions. Cortico-thalamic pathway analysis demonstrates segregation and integration of parallel pathways. The Allen Mouse Brain Connectivity Atlas is a freely available, foundational resource for structural and functional investigations into the neural circuits that support behavioural and cognitive processes in health and disease.
A central principle of neuroscience is that the nervous system is a network of diverse types of neurons and supporting cells communicating with each othermainly through synaptic connections. This overall brain architecture is thought to be composed of four systems-motor, sensory, behavioural state and cognitive-with parallel, distributed and/or hierarchical sub-networks within each system and similarly complex, integrative interconnections between different systems1. Specificgroups of neurons with diverse anatomical and physiological properties populate each node of these sub- and supra-networks, and form extraordinarily intricate connections with other neurons located near and far. Neuronal connectivity forms the structural foundation underlying neural function, and bridges genotypes and behavioural phenotypes2,3. Connectivity patterns also reflect the evolutionary conservation and divergence in brain organization and function across species, as well as both the commonality among individuals within a given species and the uniqueness of each individual brain.
Despite the fundamental importance of neuronal connectivity, our knowledge of it remains remarkably incomplete. C. elegans is the only species for which an essentially complete wiring diagram of its 302 neurons has been obtained through electron microscopy4.Histological tract tracing studies in a wide range of animal species has generated a rich body ofknowledge...