Cooperative Agreements

The brain is a massively interconnected network of specialized circuits. Three characteristics of these circuits make them particularly challenging: diversity of time scales, diversity of spatial scales, and heterogeneity. Understanding the brain therefore requires spanning these temporal and spatial scales and providing information about cell-types. We need to be able to record the activity of individual neurons across time to understand activity patterns on a millisecond timescale and how those patterns evolve with experience across hours, days, months and even years.

PROJECT SUMMARY/ABSTRACT Targeted modulation of neural activity is an essential approach in basic and clinical neuroscience research. Optogenetic proteins, such as light-activated ion channels or pumps, enable optical control of neuronal activity with exquisite spatiotemporal precision. Thus, they provide powerful means to interrogate how neural activity contributes to brain functions and alter pathological activity to treat neurological disorders. A variety of excitatory optogenetic tools have been developed to meet different needs of activation paradigms.

PROJECT SUMMARY To understand the computations in the brain, we need to monitor the activity of neural circuits at high accuracy, which requires methodologies with high spatial and temporal resolution. Non-invasive and capable of resolving subcellular structures, optical microscopy has been extensively applied in the field of neuroscience, with a variety of methods developed to image neural activity at high speed, large depths, and/or over large spatial scales.

Optimization of Clear Optically Matched Panoramic Access Channel Technique (COMPACT) for large-scale deep-brain neurophotonic interface With the advance of sensitive molecular indicators and actuators, neurophotonics has become a powerful paradigm for discovering the principles underlying neural circuit functions. However, a major obstacle of using light to study neurons located deep in the mammalian brain is the limited access depth. Even with the advance of multiphoton microscopy, the majority of implementation for imaging the mammalian brain is limited to ~ 1 mm in depth.

Neuromodulators regulate addiction, attention, cognition, mood, memory, motivation, sleep, and more through their influence on brain circuits. Classic tools for measuring neuromodulation in the brain have poor spatial and temporal resolution. This has hampered the discovery of the diverse and complex functions neuromodulation plays during behavior. Over the past few years, new indicators for imaging neuromodulator dynamics have begun to dismantle these barriers.

Abstract Groundbreaking work within the

Project Summary The dynamic adaptability of the mammalian brain to environmental changes is remarkable, as it is the complexity of the networks of neurons underlying the operations that allow for such adaptations. Although we have some understanding of the anatomical and functional basis of this, we are still lacking a detailed picture of how the modulation of neuronal activity works. What is the timing and locations of these neuromodulator release and relationship with excitatory/inhibitory circuits?

Project Summary The goal of this proposed research is to optimize a dual-use calcium ion sensor for recording single-cell activity from the entire dorsal cortex or hippocampus of freely-moving mice. It is widely accepted that optical imaging with genetically-encoded fluorescent calcium sensors is currently the only method to obtain measurements of genetically-identified neuronal populations with dense sampling.

Project Summary / Abstract The purpose of this project is to optimize circuit and system architectures of active electrode arrays which will provide low-noise, multiplexed acquisition of neural signals from thousands of electrodes. We will reduce noise by exploiting a novel current-sensing circuit approach and new multiplexing strategies, such as Code-Division Multiple Access (CDMA). We will also apply novel system level de-noising approaches using kriging.

A core goal of the BRAIN Initiative is to link neural activity to behavior which requires technology to acquire high-quality recordings of dynamic neural activity from different brain regions over time.