Research Projects

Project Summary: Widefield imaging and spatial multiplexing are crucial to advancing the field of neuroscience. Current imagers do not offer the speed and versatility needed for calcium or voltage imaging experiments. In the case of lifetime imaging the functionality is completely lacking in CMOS imagers. The problem is more subtle than it seems because it is not just a matter of brute force speed-up through technology. Speed increases come with large amounts of power dissipation and the need for faster data interfaces.

ABSTRACT Multiphoton microscopy is one of the preferred techniques for high-resolution functional brain imaging because of its remarkable depth penetration in thick tissue. In standard configurations, such imaging involves scanning a femtosecond laser focus in 3D throughout a sample. The laser power is fixed during the scan and image information is contained in the time dependence of the detected fluorescence signal. Several problems can occur with this technique.

Project summary A long-standing goal in neuroscience is to unravel complex behavior of healthy and diseased brain by analyzing the structure and dynamics of neural circuitry with single action potential resolution. While many voltage-sensitive indicators have been developed for direct imaging of cellular membrane potentials, realization of their in vivo potential is still compromised by toxicity, time resolution and signal weakness arising from nonspecific background labeling, low quantum yields, limited dynamic range and signal dampening from increased cellular capacitance.

We propose a concurrent multiphoton magnetic resonance imaging (COMPMRI) system for mouse imaging, in response to RFA-EY-16-001, BRAIN Initiative: New Concepts and Early-Stage Research for Large-Scale Recording and Modulation in the Nervous System (R21).

Summary Our goal in this project is to develop a new class of electrical recording device that complements and piggy- backs on cutting edge imaging technologies. Whereas multi-electrical recording has provided detailed measurements of neural activity with high temporal precision, it is also invasive, provides relatively low spatial resolution, and provides little information about the identity of measured neurons.

Project Summary This project seeks to develop a high density, minimally invasive optical microfiber array for long-term recording and manipulation of brain activity. Optical methods have become a cornerstone of modern brain science in animal models, and hold great potential for future human prosthetic devices. However, light scattering severely limits optical approaches for deep brain recording and stimulation. Current photometry methods of implanting optical fibers into deep brain areas work with relatively large fibers designed for the communications industry (125 μm).

This R21 grant responds to RFA-EY-17-001 “BRAIN Initiative: New Concepts and Early-Stage Research for Large-Scale Recording and Modulation in the Nervous System …for unique and innovative technologies in an even earlier stage of development … including new and untested ideas in the initial stages of conc

PROJECT SUMMARY The current state-of-the-art neural recording technology is limited by the ability to remotely and continuously deliver power to the implanted sensors. The implants have to maintain a continuous telemetry link (electromagnetic, optical or ultrasonic) to an external power source which restricts the mobility of the animal and in many instances the setup is too cumbersome for long-term experimentation and for use in small-sized animals.

Project Summary New tools for large-scale recording of neuronal activity in a living and behaving brain are essential for a better understanding of brain function, efficient analysis and treatment of neuronal disorders. Time resolved volumetric photo-acoustic imaging offers tremendous potential for large-scale brain recording due to its exquisite penetration into living tissues. Most recent developments in instrumentation for photo-acoustic neuroimaging are rapidly advancing the field with ever increasing resolution, sensitivity, field of view and frame rates.

Direct readout of spiking and subthreshold voltage activity from genetically-specified neural populations will facilitate major advances in our understanding of neural computation at the network level. For this reason, developing a genetically encoded voltage indicator (GEVI) with adequate speed, membrane localization, and brightness to report action potentials in mammalian cells has been a major goal in neuroscience for the past two decades.