Seven Caltech Faculty are Principal Investigators on NIH BRAIN Grants

Seven Caltech researchers are principal investigators on eight new neuroscience grants from the National Institutes of Health's Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative.

"Ultrasonic Genetically Encoded Calcium Indicators for Whole-Brain Neuroimaging"

Mikhail Shapiro, Professor of Chemical Engineering

"Imaging neural activity on a brain-wide scale is a major technology goal of the BRAIN Initiative. To achieve this goal, we will develop ultrasonic genetically encoded calcium indicators, which will allow the activity of genetically defined neuronal populations to be imaged with ultrasound – a deeply penetrant imaging modality with high resolution and wide coverage. This will enable the study of healthy and diseased neural circuits in model organisms, and facilitate the development of more selective treatments for neurological and neuropsychiatric disease." —Public Health Relevance Statement

"Stability and Robustness of Hippocampal Representations of Space"

Athanassios Siapas, Professor of Computation and Neural Systems;

John C Doyle, Jean-Lou Chameau Professor of Control and Dynamical Systems, Electrical Engineering, and Bioengineering;

Carlos Lois, Research Professor of Biology

"This project focuses on understanding how brain circuits critical for memory formation balance the need to preserve prior knowledge with the necessity to continuously learn new information. The balance between stability and plasticity may be disrupted in aging and in brain disorders such as Alzheimer's disease, and this project will provide a quantitative basis for studying such imbalance and its consequences." —Public Health Relevance Statement

"Minimally Invasive Ultrasonic Brain-Machine Interface"

Richard Andersen, James G. Boswell Professor of Neuroscience; T&C Chen Brain–Machine Interface Center Leadership Chair; Director, T&C Chen Brain–Machine Interface Center;

Mikhail Shapiro, Professor of Chemical Engineering

"The most advanced techniques for large-scale neural recording and brain-machine interfaces (BMIs) are currently invasive, causing damage to living brain tissue, and inviting significant risk for infection. The proposed work describes the development and implementation of the first BMI based on functional ultrasound (fUS) imaging - a recently developed minimally invasive (epidural) neuroimaging technique combining high spatial and temporal resolution with deep brain coverage. In this project, we will push the limits of fUS imaging as a technology for online large-scale chronic recording of neural activity by developing minimally invasive and implantable ultrasonic BMIs, creating new opportunities for neuroprosthetics and fundamental neuroscientific inquiry." —Public Health Relevance Statement

"Circuit basis of social behavior decision-making in a subcortical network"

David Anderson – Seymour Benzer Professor of Biology; Tianqiao and Chrissy Chen Institute for Neuroscience Leadership Chair; Investigator, Howard Hughes Medical Institute; Director, Tianqiao and Chrissy Chen Institute for Neuroscience

"The proposed research is aimed at developing and applying new approaches to understanding how mammalian subcortical brain circuits control evolutionarily conserved naturalistic social behaviors, which may be disrupted in human psychiatric disorders. Our objective is to construct better, high-resolution maps of neural activity dynamics in the brain during social behavior, by imaging from multiple brain sites in a circuit, and using machine learning algorithms (AI) to automatically extract and measure social behavior from video recordings, thereby enabling precise, quantitative correlations between distributed brain activity and behavior. We also propose to examine how intruder sex and behavioral decisions are computed and transformed as they are propagated through the network." —Public Health Relevance Statement

"Dissecting sodium appetite circuits in the mammalian brain"

Yuki Oka – Professor of Biology and Chen Scholar; Investigator, Heritage Medical Research Institute

"Overconsumption of sodium is a serious risk factor of cardiovascular and cognitive malfunction. This project will examine the brain circuit that mediates sodium appetite and consequent ingestion. The proposed research is relevant to public health because it will provide insights into the function and dysfunction of sodium regulatory mechanisms that optimizes dietary sodium intake." —Public Health Relevance Statement

"Interferometric Speckle Visibility Spectroscopy for Brain Activity Associated Cerebral Blood Flow Monitoring"

Changhuei Yang – Thomas G. Myers Professor of Electrical Engineering, Bioengineering, and Medical Engineering; Investigator, Heritage Medical Research Institute

"We propose to develop a novel parallel (~50 points) high temporal resolution optical cerebral blood flow (CBF) monitoring prototype. If successful, the technology will fill a vital measurement gap that existing optical, MRI, ultrasound and PET methods have not been able to address. The technology can potentially provide a way to study CBF changes in response to brain activities in a non-invasive and portable fashion." —Public Health Relevance Statement

"Sensory motor transformations in human cortex"

Richard Andersen – James G. Boswell Professor of Neuroscience; T&C Chen Brain–Machine Interface Center Leadership Chair; Director, T&C Chen Brain–Machine Interface Center

"The work proposed will lead to scientific understanding of sensory and motor functions in the human nervous system. The results will have direct relevance to the development of neuroprosthetic medical devices. Such devices can help people with severe paralysis from spinal cord lesion and other traumatic accidents, peripheral neuropathies, amyotrophic lateral sclerosis, multiple sclerosis, and stroke." —Public Health Relevance Statement

"Engineered AAV Identification, Validation, and Dissemination Pipeline for Brain Cell Type-Specific Manipulation Across Species"

Viviana Gradinaru (BS '05) – Professor of Neuroscience and Biological Engineering; Director, Center for Molecular and Cellular Neuroscience

"This project will establish an integrated platform for non-invasive and cell type-specific targeting of molecular tools with engineered AAVs in rodents, non-human primates, and human organoids representing several brain regions. The integrated tools (AAV capsids and cargo) that comprise this AAV BRAIN SENSUS (Safe and Effective Neuromodulator and Sensor Utilization across Species) will be extensively catalogued, de-risked through continuous validation, and disseminated throughout the neuroscientific community to catalyze interrogation of brain function from cell to circuit across species, and ultimately contribute toward cures for brain diseases." —Public Health Relevance Statement