Research Projects

 DESCRIPTION (provided by applicant): The ideal neuroimaging technique would provide exquisite structural detail and also provide functional information, with high spatial and temporal resolution. Optical coherence tomography (OCT) is an optical imaging technique in which light from a low coherent source illuminates tissue and reflectivity of internal microstructures at different depths is measured by an interferometer. OCT is capable of micrometer-spatial and millisecond-temporal resolutions, without the use of exogenous contrast agents (hence "label-free").

 DESCRIPTION (provided by applicant): This proposal embodies the rational design, high throughput screening, and in vitro characterization of novel neuronal actuators. The starting point for our endeavor is an ionotropic channel that launched the optogenetic revolution. We are confident that the highly original and comprehensive development scheme we have outlined will yield a new set of transformative tools for functional brain analysis.

 DESCRIPTION (provided by applicant): A central goal in neuroscience is to identify cellular ensembles supporting mental and behavioral states, but these ensembles cannot be defined a priori. The dentate gyrus (DG), for example, contains more than 1M granule cells, which are essentially indistinguishable from each other, but less than 5% of these seemingly identical neurons are active during any one behavioral event, suggesting that the associated mental states are each mediated by a small subset of neurons.

 DESCRIPTION (provided by applicant): The overarching goal of this project is to develop molecular tracers for imaging neuronal voltage changes deep in the brain. Photoacoustic imaging holds great promise to analyze the structure and function of neural circuitry deep in the brain, yet no compatible tools have been developed to probe neuronal activity. Therefore, we bring together unique resources in molecular tracer engineering and tissue-penetrating photoacoustic imaging technology to develop a toolbox of 'voltage tracers' for probing neural electrical activity.

Electrical activity in the brain is a direct correlate to neuronal activity. Existing technology can record electrical activity on a millisecond scales through invasive placement of electrodes within the brain or non- invasively, using subdermal electrodes. Such recordings can be used to study brain function, diagnose diseases of the brain or to directly control external machinery (a.k.a. Brain Computer Interface or BCI). Currently, the low fidelity, sensitivity, poor spatial resolution, and susceptibility to noise limits the use of subdermal EEG.

SUMMARY We propose an ultra-miniature as well as extremely compliant system that enables massive scaling in the number of neural recordings from the brain while providing a path towards large-scale neural recordings and truly chronic brain-machine interfaces (BMI). This will be achieved via two fundamental technology innovations: 1) 10 – 100 μm scale, free-floating, independent sensor nodes, or neural dust, that detect and report local extracellular electrophysiological data, and 2) a subcranial mm-scale interrogators that establish power and communication links with the neural dust.

PROJECT SUMMARY/ABSTRACT The brain's control of our thoughts, feelings, and behaviors stems from neural circuits, which perform logical operations based on the temporal patterns of neural activity and the connectivity of the neurons as the circuit traverses the brain. Recent studies have produced many strategies for visualizing and controlling a circuit's neural activity. In some cases, specialized microscopy systems have enabled imaging of entire brain volumes on the timescale of neural activity and during behavior, enabling the reconstruction of neural circuitry at cellular resolution.

Project Summary The long terms goal of this project is to enable the control of large networks in the brain using neurostimulation technologies, a key focus of the BRAIN initiative.

Optimal calcium imaging with shaped excitation Understanding information flow in the brain is dependent on simultaneously recording the activity of large neuronal populations. It seems impossible to interrogate neurons serially, and still image large populations of neurons with high temporal resolution and high signal to noise. This is linked to the inverse relationship between volume scanned, and the signal collected per voxel, at fixed spatial and temporal resolution. However, this is not a hard limit.

SUMMARY: Understanding the mechanisms by which the living brain derives perception, cognition and behavior requires the ability to record and control electrical activity in many neurons simultaneously. Completely reconstructing the pattern of neural activity that mediates a specific neural operation is critical for fully understanding its underlying mechanism. This requires an approach that can measure neural activity on a large scale with high spatial and temporal resolution.