Monitor Neural Activity

In dendrites, Ca2+ is critical in determining how neurons respond to incoming excitation. While numerous studies have focused on how dendritic Ca2+ relates to behaviorally-relevant neuronal and circuit activity using correlative observations, there is currently no method to precisely manipulate Ca2+ in neurons in vivo and thus causally test its role in circuit function and behavior. In non-neuronal cells, mitochondria can act as sinks for Ca2+ released from the endoplasmic reticulum (ER) by forming direct contacts with these concentrated intracellular Ca2+ stores.

Project Summary and Abstract A major obstacle to understanding the link between behavior and neuronal activity is the difficulty of electrophysiologically recording the activity of large neuronal populations without limiting visual access. Electrode arrays directly measure electrical signals and offer significantly greater temporal resolution than optical fluorescence techniques, but the resulting obstruction of optical access limits the ability to pair electrode arrays with optogenetic stimulation and calcium imaging.

ABSTRACT Depicting the specific neuronal identity and connectivity underlying particular brain function remains a central goal for neuroscience. For over a century, neuroanatomy has continued to play critical roles in referencing a neuron's synaptic contact, dendritic morphology and axonal projection to its connectivity. The advances of genetic probes, optical imaging modalities and computer technologies permit monitoring and manipulating neuronal activity in living animals with unprecedented precision and scale.

PROJECT SUMMARY Every part of the brain is composed of dense tangles of heavily-interconnected neurons of many different types, each playing completely different roles in the circuitry. Rabies viral vectors have become indispensable tools for revealing the organization of this otherwise generally indecipherable jumble, because they allow the identification of synaptically-connected networks of neurons within the tissue.

Project Summary The development of trans-synaptic viral tracers is an important component of the BRAIN Initiative. At present, the lack of viral-based anterograde monosynaptic tracing tools with high signal strength and low toxicity is a gap in neuroscience.

Project Summary/Abstract Reuse of existing neuroscience data relies, in part, on our ability to understand the experimental design and study data. Historically, a description of the experiment is provided in textual documents, which are often difficult to search, lack the details necessary for data reuse, and are hampered by differences in terminologies across related fields of neuroscience.

Project Summary/Abstract ! Most genetic recorders described so far utilize the CRISPR/Cas9 system to leave a unique genetic scar in each cell that can be traced in daughter cells. However, since these systems are largely deletion based, there is a finite number of events and lineages that they can be used to trace. Hence all these recorders are fundamentally restricted in the number of lineages they can trace since development in mammals is a prolonged process, with radial glia in the brain dividing greater than 50 times.

Abstract The goal of this project is to develop an archival data format and a formal task specification language to serve as standards for describing behavioral experiments. Because different laboratories use different behavioral systems, hardware, and software, it has been difficult to communicate behavioral task design, share data, or reproduce experiments.

Neuroscientific data contain information from an incredible diversity of species, are generated by a plethora of devices, and encapsulate the results of scientific thinking and decision making. Most of this generated data remains confined within laboratories and is not accessible to the broader scientific community. The research projects awarded under the Brain Initiative are generating a diverse collection of data that can transform and accelerate the pace of discovery. These datasets are large--ranging in size from GBs to PBs-- and represent diverse data types and assorted metadata.

To take advantage of recent and ongoing advances in intensive and large-scale computational methods, and to preserve the scientific data created by publicly funded research projects, data archives must be created as well as standards for specifying, identifying, and annotating deposited data. The value of and interest in such archives among researchers can be greatly increased by adding to them an active computational capability and framework of analysis and search tools that support further analysis as well as larger scale meta-analysis and large scale data mining.