Research Projects

Project Summary Large-field-of-view high-throughput two-photon endoscope to image neuronal activity Development of miniaturized optical endoscopes have enabled visualization and recording of neural activity in freely-behaving animals. Two-photon endoscopes have excellent signal-to-background ratio, and can image deep into the tissue. It has a good optical sectioning and low phototoxicity. However, two-photon endoscopes have a very limited field of view and imaging throughput, and cannot typically perform axial refocusing for 3D imaging.

Abstract There is a growing interest to effectively combine optical approaches with electrophysiology at large scale and with great precision to fully leverage the complementary spatial and temporal resolution advantages of both techniques. It is also widely recognized that device softness and compliance are important attributes to dramatically lower tissue injury and irritation and maintain signal quality over time.

The large-scale dynamics of neural circuitry depend on interactions among numerous neurochemical spe- cies that play functionally distinct roles throughout the brain. Understanding the spatial and temporal character- istics of chemical signaling is thus crucial for building mechanistic models of brain function. Our laboratory has introduced paramagnetic neurotransmitter sensors that enable functional analysis of neurochemical phenomena over large fields of view by molecular-level functional magnetic resonance imaging (molecular fMRI).

ABSTRACT Micromagnetic stimulation (µMS) has several advantages over electrical stimulation. First, µMS does not require charge-balanced stimulation waveforms as in electrical stimulation. In µMS, neither sinks nor sources are present when the time-varying magnetic field induces a current. Thus µMS does not suffer from charge buildup as can occur with electrical stimulation. Second, magnetic stimulation via µMS is capable of activating neurons with specific axonal orientations.

PROJECT SUMMARY/ABSTRACT A wealth of new tools can directly control output of specific neurons on fast (e.g., optogenetic) or sustained (e.g., chemogenetic) time scales. In contrast, almost no methods exist for selectively modulating communication between defined cells at the synaptic level, which is key to understanding how functional connectivity creates percepts, engrams and actions. Here, we advance a novel strategy for selectively modulating synaptic transmission, Interluminescence.

SUMMARY A major goal of the BRAIN initiative is to develop neural imaging technologies enabling whole-brain imaging of specific molecular signals such as neuronal calcium.

ABSTRACT Optical imaging holds tremendous promise in our endeavor to understand brain functions. The major challenges for optical brain imaging are depth and speed. Due to optical aberrations and tissue scattering, the penetration depth and imaging speed of optical microscopy in the brains (e.g., mouse) is limited.

ABSTRACT We propose to develop novel neurorecording devices using sequential thin-film transistors that are capable of recording and stimulating brain activity with thousands of channels using only 8 wires and to demonstrate broadband recordings with large area coverage in fully awake, chronically implanted mice performing a decision task.

Abstract Brain-machine interfaces (BMIs) are one of the key motivating applications for the BRAIN Initiative’s drive to develop innovative technologies for large-scale recording of neural activity, benefiting not only BMI, but many other neuroscience studies.

Project Summary To further our understanding of the function of neural circuits, there is a need for new tools that can collect simultaneous measurements from large populations of neurons involved in a common neural computation and provide precise functional modulation. Optical imaging in awake animals expressing calcium or voltage indicators provides real-time functional and spatial information from individual neurons within local neural circuits.