Theory & Data Analysis Tools

PROJECT SUMMARY Efforts to understand the mechanisms of brain-based disease have been hindered by the limited ability of animal models to reflect the full complexity of human brain and behavior. Brain organoids represent a potential solution, allowing scientists to model human neurodevelopmental and disease processes in-vitro. These multicellular, three-dimensional tissue structures are derived from induced pluripotent stem cells and self-organize to recapitulate aspects of human cortical development.

Project Summary Towards the end of nervous system development, neural circuits are extremely plastic. Small perturbations during this time can cause lifelong circuit and behavioral changes. Not surprisingly, mounting evidence suggests that several neurodevelopmental disorders, including autism spectrum disorder and epilepsy, have origins in defective late neural circuit formation. During this late stage, neural circuits refinement takes place, and components of the mature behavior gradually appear. As this occurs, stimulus-independent bursts of activity sweep through neuronal populations.

PROJECT SUMMARY/ABSTRACT How the brain generates the correct number of neurons and how these neurons determine the size of their arbors to innervate the receptor field is a critical question in neurobiology. The Drosophila visual system is hard wired and iteratively organized into columns, providing an excellent model to answer these questions. Drosophila medulla multicolumnar neurons exhibit 5 to 750 neurons per cell type; each neuron class possesses a distinct morphology and projects its arbors across multiple columns in the optic lobe.

Project Summary There is currently an unmet need for accurate model systems of the human brain to study its cellular and molecular features. The cerebral cortex regulates our cognitive capacity, yet the cellular diversity, circuit formation, and function that establish this potential, largely remains a mystery. The cortex is expanded in humans compared to other species; it contains more cellular diversity and abundance, making model organisms limited for translational studies.

PROJECT SUMMARY The goal of this project is to build an open-access recombinant antibody/affinity reagent resource for the neuroscience community called NABOR (Neuroscience AntiBody Open Resource).

PROJECT SUMMARY/ABSTRACT This project aims to disseminate validated technologies and resources of the National Center for Microscopy and Imaging Research (NCMIR) at UC San Diego to advance the completion of strategic goals of the BRAIN Initiative.

PROJECT SUMMARY Lack of standards for neurophysiology data and related metadata is the single greatest impediment to fully extracting return on investment from neurophysiology experiments. One of the greatest questions in science today is understanding how the brain works and gives rise to thoughts, memories, perception, and consciousness.

PROJECT SUMMARY A key problem in neuroscience is understanding how internal and external information are integrated in the brain to produce sensory experiences, cognition, and behavioral responses. This integration relies on flexible modulation of sensory processing in response to behavioral states like motivation, attention, and arousal. Neurons in the basal forebrain are key mediators of these behavioral states. At the same time, basal forebrain neurodegeneration in Alzheimer’s and Parkinson’s disease is associated with deficits in both cognitive and sensory processing.

Project Summary High-throughput profiling of hundreds of thousands of cells in the central nervous system (CNS) is currently underway.

Project Summary This application describes a 5-year plan to investigate the neural dynamics that underpin distortion in memory, integrating computational modeling approaches with functional neuroimaging (fMRI) and non-invasive brain stimulation techniques (TMS). The candidate, a cognitive neuroscientist with a background in memory consolidation and experience in fMRI and TMS methods, seeks new training in computational modeling and model-based fMRI analysis under the mentorship of Dr. Anna Schapiro and Dr. Sharon Thompson-Schill.