Theory & Data Analysis Tools

PROJECT SUMMARY Significance: Neural circuit assembly requires activity-dependent refinement of circuit architecture (e.g. plasticity) to produce stereotyped behavior. Neurons are particularly susceptible to functional and structural plasticity during early developmental windows called critical periods. It is clear that failure to terminate critical period plasticity adversely affects mature circuit function in both animal models and humans (e.g. autism and epilepsy), yet the mechanisms that close critical periods are largely unknown.

Project Summary/Abstract Alternative splicing of pre-mRNAs is extensively employed by the nervous system to expand the transcriptomic manifold. Regulated in specific cellular contexts by multiple RNA-binding proteins (RBPs), this process is a major contributor to cellular identity that acts orthogonally to transcriptional regulation and has been implicated in many neurodevelopmental disorders.

Project Summary/Abstract: Glial cells collectively outnumber neurons in the vertebrate brain, but mechanistic understanding of their molecular subtypes and functions is lacking. Ependymal cells, ciliated epithelial cells that line the brain ventricles and produce laminar flow of cerebral spinal fluid (CSF) with their many motile cilia, are one such enigmatic group of glia. Relatively little is known about them, even compared to other glial cell types.

PROJECT SUMMARY Insufficient sleep, sleep disorders, and resulting problems with health and cognition are increasingly common in the United States. Many sleep disorders may be associated with abnormal sleep homeostasis: an innate regulatory process that balances sleep need, sleep intensity, and sleep amount as a function of prior time spent awake. Sleep homeostasis requires a feedback circuit to maintain the system within defined limits. However, the cellular components and protein signaling pathways of this feedback circuit remain incompletely defined.

Advancing Bio-Realistic Modeling via the Brain Modeling ToolKit and SONATA Data Format One of the major goals of the BRAIN Initiative is to distill complex, multi-modal data into predictive frameworks via theory/modeling.

Since its invention in the early 90s, functional magnetic resonance imaging (fMRI) has revolutionized our un- derstanding of the human brain. Functional MRI may be used to observe brain function during a specific motor or cognitive task, or at “rest” (resting-state fMRI). The latter produces so-called “functional connectivity” maps that may provide a new window into human cognition. There is currently a large, world-wide effort underway to discover potential research and clinical uses of such connectivity maps.

The BRAIN Viral Vector Service and Distribution Core will serve as a resource for the maintenance, propagation, and distribution of viral vectors that are used by neuroscientists for neural circuit identification and manipulation, as well as for preclinical translational studies.

Traditional file-based neuroimaging data management and integration strategies have shown increasing limitations in accommodating the meteoric growth in both the scale and complexity of today’s neuroimaging data. The sophisticated software and hardware pipelines required in many of today’s neuroimaging studies have produced numerous platform-specific data files that are increasingly difficult to parse, exchange, and understand by the broader research community.

PROJECT ABSTRACT The nervous systems of animals are comprised of neurons connected by a large number of synapses. The resulting neural networks underlie animal behavior and contribute to the storage of learned information in many species. In humans, the miswiring of neural networks likely results in disorders of behavior, learning, and thought. For all these reasons, understanding the development, organization, and disruptions in neural circuits is vital. The goal of connectomics is to produce and study the maps of neuronal connections within nervous systems.

PROJECT SUMMARY Stroke-causing illness, disability, and early death is set to double worldwide within the next 15 years. Despite physical therapy, about 50% of stroke survivors have impaired hand function, which strongly impacts activities of daily living and independence; novel treatment methods are urgently required.