Monitor Neural Activity

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.

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.

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.

SUMMARY Animal behaviors are orchestrated by the sophisticated nervous system, which is dynamically regulated by neuromodulators including lipids and neuropeptides. Endocannabinoids (eCBs) are neurolipids exist broadly in the brain and regulate learning and memory, addiction, pain sensation, and food intake. Among neuropeptides, cholecystokinin (CCK) is involved in nutrient sensing, food intake, and sleep regulation, and oxytocin (OXT) and vasopressin (AVP) play important roles in various aspects of social behaviors.

PROJECT SUMMARY . There are numerous clinical needs for a technology that can modulate nervous system activity noninvasively and focally, with clinically-relevant spatial and temporal precision, with a robust and predictable mechanism of action, and that could act on any of the varied modes of neural signaling: excitatory, inhibitory, and neuromodulatory. We have developed exactly such a technology by combining focused ultrasound and drug delivery nanotechnology.

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.

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 (

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.

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.

Project Summary / Abstract Lennox-Gastaut Syndrome (LGS) is a devastating form of childhood onset epilepsy with cognitive dysfunction and very frequent generalized onset seizures (GOS) often leading to injury. Driven by the lack of effective therapies and the demonstrated safety and efficacy of brain-responsive stimulation for medically intractable focal onset seizures (FOS), this study will test whether brain-responsive neurostimulation of thalamocortical networks (RNS-TCN) is a feasible strategy to treat LGS.