Research Projects

In vivo Imaging of Neuroactivity in the Deep Forward Scattering Regime Using Speckle Identification and Demixing (SPID) Microscopy

PROJECT SUMMARY Optical imaging of neuronal activity in the mammalian brain at depth and at high spatial and temporal resolution remains a key challenge in neuroscience. This is because tissue scattering eliminates directional information carried by photons, with a characteristic length scale of hundreds of microns. As a result, the remaining unscattered, or “ballistic” component of light decays exponentially with depth.

Ultra-flexible μLED Optoelectrode Platform for Brain Circuit Mapping: a Longitudinal, Minimally Invasive Tool

Project Summary Significance: Neuroscientists have set ambitious goals for electrophysiology and stimulation technology but these tools continue to lag behind. The mission is to achieve a scale at least on the order of the local neural circuits and to do so with a technology that does damage this circuit.

A Fully Ultrasonic Approach for Combined Functional Imaging and Neuromodulation in Behaving Animals

PROJECT SUMMARY Two very recent advancements have been transforming the field of medical ultrasound. First, the revolutionary discovery of ultrasound neuromodulation, which non-invasively targets and modulates activity in specific regions of the brain. Second, contrast-enhanced super-resolution, which can image microvessels at resolutions as small as ten microns, an order of magnitude smaller than the ultrasound diffraction limit, and at greater depths.

Opto-Crown: Transparent skulls with embedded optics for cortex-wide cellular resolution imaging in freely moving mice

PROJECT SUMMARY The activity patterns of millions of neurons organized in circuits distributed across multiple brain regions mediate our interaction with the outside world. Current technologies for neuronal activity mapping such as electrodes, or optical modalities such as microscopic imaging of genetically encoded voltage and calcium influx sensors, can only record from 100s to 1000s of neurons simultaneously. Practical technologies that enable simultaneous mapping of neuronal activities from large brain volumes at cellular resolution currently do not exist.

Multimodal Stainless Steel Neural Interfaces for Large-scale Recording and Modulation in Large Animals

Project Summary In this proposal a course of research is proposed to design and implement high-density multimodal (electrical and optical) neural probes on stainless steel for robust, reliable and large-scale recording from thousands of neurons in large animal (primate) brains. The neocortex consists of millions of neurons that form circuits that mediate perception, motor control, memory, and behavior.

Wireless Magnetomechanical Neuromodulation of Targeted Circuits

Abstract Scalable approaches to modulate neural activity during complex behaviors are essential to basic study of normal and aberrant brain function. Here we aim to develop a wireless magnetomechanical neuromodulation technique suitable for remote excitation of genetically identifiable neuronal populations. This approach will rely on the ability of anisotropic synthetic magnetic nanodiscs to transduce torques to cell membranes in weak slow-varying magnetic fields.

Head-mounted Photoacoustic Imaging of Deep-brain Neural Activities in Freely Behaving Animals

Abstract To capture the normal brain functions, it is critically important to record the neural activities in freely-behaving animals, with high resolution, high speed, and high throughput. So far, our knowledge about neuronal activity of awake animals mainly relies on electrode recording, which, however, is invasive. Optical imaging techniques have been widely used to visualize activity of a large number of neurons in mouse models using fluorescent membrane voltage or calcium indicators. However, limited by the penetration depth (

Sonogenetic control of neurons in a large volume of the rodent brain

Abstract A key challenge in neuroscience is the development of methods to non-invasively manipulate specific neuronal cell types in vivo. While recent opto-, chemo- and magneto-genetic approaches have revolutionized our ability to control both neuronal and non-neuronal cell types, they each suffer from critical drawbacks, including the inability to deliver light to targets deep within the brain or to large volumes of the brain (opto-), and the lack of precise temporal control for both chemo- and magneto-genetic approaches.

Photoactivatable systems for controlling transcription and ablating synapses.

The advent of optogenetic tools for controlling neuronal function with light has led to dramatic advances in the understanding of the anatomy and function of neural circuits. Optogenetic tools for controlling transcription and modifying neuronal connectivity could also be extremely useful for interrogating neuronal circuits. However, these tools are based on photo-activatable complexes, and all current versions of such complexes, which depend on photo-isomerization, have a small amount of background activation in the dark, which makes them difficult to implement in vivo.

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