Circuit Diagrams

A new approach to biological recording of lineage hierarchy in primate brains

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.

Generating a formal set of collaborative standards for sharing behavioral data and task designs to enable reproducibility in neuroscience

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.

DANDI: Distributed Archives for Neurophysiology Data Integration

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.

BRAIN INITIATIVE RESOURCE: DEVELOPMENT OF A HUMAN NEUROELECTROMAGNETIC DATA ARCHIVE AND TOOLS RESOURCE (NEMAR)

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.

A Massive Library of AAVs to Target Transcriptionally-Defined Primate Cell Types

Here we will identify nonhuman primate (NHP) neuron types and build an extensive toolbox of vectors for circuit- based neuroscience studies. NHPs share substantial neuroanatomical, genetic, and behavioral homology with humans, and therefore they are indispensable for investigating the neural circuit basis of cognition and devising therapies to treat neurological and psychiatric disorders. Despite the importance of NHPs, we lack the tools to analyze and manipulate complex circuits in the primate brain.

Development and validation of AAV vectors to manipulate specific neuronal subtypes and circuits involved in epilepsy and psychiatric disorders across mammalian species.

PROJECT SUMMARY In this proposal we aim to identify gene regulatory elements that permit the targeting and manipulation of brain circuit models of human brain function. Gaining genetic access to specific neuron populations in nontransgenic animals and humans would enable targeted circuit modulation for hypothesis testing and provide a means to evaluate the safety and efficacy of circuit modulation for the treatment of epilepsy and psychiatric disorders.

Developing genetically-encoded detectors for neuropeptide release based on class B G-protein coupled peptide receptors

Abstract Synaptic transmission is mainly mediated by classical neurotransmitters such as glutamate and g-amino butyric acid (GABA) which transduce fast information flow in the brain. This process is tightly regulated by neuromodu- lators including monoamines and neuropeptides.

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