Research Projects

Abstract Understanding brain function requires the ability to record simultaneously from thousands or tens-of- thousands of neurons contributing to the dynamic activity in a neural circuit. CMOS based electrode technology constitutes the only means to electrically interact with living systems beyond this scale and at sub- millisecond time resolution, but suffers from the limited recording depth and the invasiveness of silicon wafer which might prohibit their use in human experimentation.

Project Summary A primary focus of the

PROJECT SUMMARY Here, we will generate photoswitchable and photoactivatable bioluminescent (PS-BL and PA-BL) light sources. These constructs will be implemented to facilitate highly selective and “reprogrammable” modulation of neural ensembles. The PS-/PA-BL approach allows rapid selection (minutes), quick re-set (hours), and can be implemented across depths by selective 2-Photon activation. Neural control will be implemented by using PS-BL light to drive optogenetics (PS-BL-OG), a powerful modulation strategy.

PROJECT SUMMARY Optical imaging methods are well-established in neuroscience, but high-speed, high- resolution volumetric imaging of neural activity in deep tissue remains a challenge. A number of techniques address limited aspects of this goal, and most are applicable primarily to acute preparations. We propose to develop and test a novel approach to achieve three-dimensional “deep-tissue” imaging for high spatial and temporal resolution neural recording by combining aspects of embedded optical probes with computational imaging techniques.

Recent advances in pluripotent stem cell technology have enabled generation of neuronal cell lines and cerebral organoids from human embryonic stem cells (hESCs) as well as human induced pluripotent stem cells (hiPSCs) derived from peripheral tissues. These organoids are self-assembled, 3D cellular structures that resemble early developmental stages of the human brain opening unprecedented opportunities for investigation of human neuronal network-level dysfunction underlying developmental brain disease.

PROJECT SUMMARY/ABSTRACT Protein ticker-tapes for brain-wide neural recordings Behavior emerges from the interacting activity of widely distributed ensembles of neurons; but all existing tools for measuring brain activity sample only a small subset of these dynamics. Here we propose a protein-based approach to record brain-wide dynamics of two key measures of neural activity: immediate early gene (IEG) expression and Ca2+ concentration. This proposal focuses on in vitro proof of concept; follow-up efforts will focus on in vivo application if warranted. Tree rings and ticker tapes.

Neuro-flakes: Direct Voltage Imaging of Neural Activity with Atomically-thin Optoelectronic Materials Recording electrical activity of neural populations with high resolution is essential to investigate neural circuits and cognitive functions. Although electrophysiology remains to be a widespread tool in neuroscience, it lacks practical scalability and chronic stability needed to tackle large-scale information processing in the brain.

Nanosecond pulsed electric field (nsPEF) is a new modality for neuromodulation, with unique capabilities qualitatively different from the conventional electrostimulation.

Project Summary Minimally invasive neural modulation at sub-millimeter spatial resolution remains a critical yet unmet biomedical need. Researchers have explored a broad spectrum of electromagnetic wave and developed wireless neuromodulation methods. Due to its long wavelength, transcranial magnetic stimulation does not provide sufficient spatial resolution to target a functional unit such as a single ocular dominance column in the visual cortex or a diseased peripheral nerve.

Implantable interfaces for neuromodulation is necessary to advance fundamental neuroscience research, develop new treatments for neurological disorders, and create efficient breakthrough neuroprosthetics. However, modern implants based on multi-electrode arrays suffer from low spatial resolution, high invasiveness with complicated implantable procedures, the need for a chronic opening for connecting wires, and substantial foreign body reaction, eventually leading to device failure.