Brain science tools have advanced in several distinct directions. Advanced tools in molecular biology now allow neuroscientists to study distinct patterns of gene expression in individual neural cells, leading to the potential for a comprehensive atlas of cell types. In parallel, tools that allow for the visualization and manipulation of neural circuitry, including targeted stimulation of specific cell types through tools such as opto- and chemo-genetics, have provided unique tools to study circuit function in vivo. These tools in particular have been aided by advances in in vivo optical microscopy in animal models, which have advanced to the point of measuring thousands of activated cells during complex behaviors in model systems. At the same time, tools to study the human brain have continued to advance our ability to interrogate network functions across the entire brain, albeit at macroscopic spatial and more limited temporal resolutions. Nevertheless, there is a growing anticipation of convergence of these approaches – microscopic imaging in animal models now can map much of the entire mouse cortex, for example, which has revealed a rich dynamic structure of activity at mesoscopic scales heretofore predicted from models of emergent properties of networks but now directly measured. In parallel, human investigations have pushed the limits of our non-invasive functional imaging and stimulation tools to the point where the system level features we have observed for two decades are now beginning to reveal their own underlying mesoscopic structures – for example, activity in individual cortical columns and lamina within the visual system, and dynamic maps of electrophysiological activity which can be directly modeled at neuronal scales. Hence from the “bottom-up,” and from the “top-down,” mesoscale mapping is the next frontier.

It is the goal of the Center for Mesoscale Mapping, the CMM, to push this convergence of microscopic and macroscopic imaging tools forward for human translational neuroscience by developing and applying the next generation of tools to study the spatial distribution and temporal orchestration of mesoscopic events in the human brain. Our tools will provide our Collaborative and Service User community with important “missing links” between the advances in human cognitive neuroscience at the “system level” and the enormous strides in circuit functional characterization seen in animal models. Our Collaborators will each bring their own unique insights to further develop and apply these tools, offering distinct measures of human brain structural and functional properties in a variety of normal and disease settings, while our Service Users will utilize these tools to better understand the human neural systems and particularly human disease states ranging from multiple sclerosis to Alzheimer’s disease to depression and schizophrenia. Finally, our Center will seek to disseminate these tools, through open-source software and industrial partnerships for hardware, and to train a new generation of human neuroscientists in the use of our advanced tools to explore the human brain at this next frontier. By tackling the most challenging and least understood organ up front – the human brain – the CMM will maximize the impact of our tools and establish a framework that can ultimately be extended beyond the brain to multiple other organs, with the long term vision of providing tools that will enable the seamless integration of microscopic and macroscopic information for all of human systems biology. The unique structure of the NIBIB Biomedical Technology Resource Centers will allow us to develop and disseminate these advanced technologies with a focus on their widespread use both here in Boston and throughout the nation, and for basic science and, importantly, clinical translational investigations, something no other mechanism supports.