Research Projects

Project Summary Recent years have seen major breakthroughs in methodology for studying two complex yet fundamental aspects of brain structure: synaptic connectivity patterns and the heterogeneous distribution of molecules. Due to an ongoing technical barrier that has endured for decades, advances in circuit imaging and molecular imaging have progressed almost entirely in parallel, and there are still no routine methods for integrating molecular information into synaptic circuit maps.

PROJECT SUMMARY Identifying the cell types that make up each region of the brain and the patterns of synaptic connections through which they are linked is key to understanding how neural circuits give rise to all perception, cognition, and behavior. Rapid improvements in optical, molecular, and computational technologies are enabling large- scale projects aiming to comprehensively map the cell types that comprise the mammalian brain. Nevertheless, defining the microconnectivity of the thousands of cell types in the brain remains challenging due to a lack of scalable methods.

ABSTRACT A comprehensive census of neural cell types in the brain, together with molecular-genetic resources for cell-type specific labeling, is revolutionizing our ability to detect and monitor age, disease, and experience-dependent changes in neural connectivity.

The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative promotes the development and application of technologies to describe the temporal and spatial dynamics of cell types and neural circuits in the brain.

PROJECT SUMMARY Brain image data collected by the neuroscience community will continue to grow dramatically in the next 5-10 years as the push to image physically larger volumes, such as whole brains from humans and other primates, becomes a focus. The scientific community, with the support of

Project Summary Understanding cell-type-specific gene functions, expression dynamics, and regulatory mechanisms in complex brains is still challenging.

PROJECT SUMMARY/ABSTRACT Intracranial recordings in patients undergoing neurosurgical interventions provide a unique opportunity to directly access, study, and learn about both normal human brain function and neuropsychiatric disease. Because of their value, the

PROJECT SUMMARY Neurons in the visual cortex form an intricate connectivity structure and topographic arrangement. The structural and morphological organization of the neurons is known to constrain its functional properties. To understand these constraints, it is necessary to generate large-scale anatomical and functional measurements of the brain. Ongoing efforts in electron microscopy (EM) and fluorescent microscopy promise to massively accelerate the speed of generating such data.

Project Summary A key goal in neuroscience is determining how microcircuit structure predicts circuit function. An intriguing idea, supported by some theoretical models, is that variation in microcircuit composition supports functional specialization. This theory has received support from the observation of a correlation between gradients in circuit properties (receptor expression densities; inhibitory cell types) and in measurements of average intrinsic timescales of recorded activity across cortical areas.

Project Summary The neuroscience community is experiencing a revolution in its ability to share and analyze vast amounts of human brain imaging data, with support from the BRAIN Initiative and other substantial data-sharing efforts.