Research Projects

PROJECT SUMMARY/ABSTRACT The goal of this proposal is to assess the feasibility of a non-invasive nanoparticle platform for tool delivery to the brain. We propose to generate mixed-surface, cystamine core PAMAM dendrimers with unique features. By significantly expanding the cargo size, cell populations in the brain can be targeted genetically utilizing regulatory elements exceeding the size limit of current tools. In addition, increased cargo size will allow delivery of multiple smaller molecules at specific optimal ratios, an increasing need with newly developed multi- component systems.

ABSTRACT Scale is a fundamental obstacle in linking neural activity to behavior. While perception and cognition arise from interactions between diverse brain areas separated by long distances, neural codes and computations are implemented at the scale of individual neurons.

PROJECT SUMMARY To understand the cellular basis of cognition, behavior and pathology, it is necessary to map the different participating brain regions and circuits that participate during the different biological processes and do so I the same animals. I propose to reach this goal by establishing a novel genetic method for full brain scale recording of integrated cellular activity in living mammals.

PROJECT SUMMARY Development of non-invasive tools for activating deep brain structures is critical for causally manipulating neural function in humans. Furthermore, such method, if able to elicit long-term plastic changes in neural circuits, will aid in functional recovery of neural function. One of the promising non-invasive neural modulation technique that has a potential to activate deep brain structures in a focal manner is ultrasound. Several groups have demonstrated that ultrasound can lead to neural activation, alter sensory responses, or cause behavioral outcomes.

PROJECT SUMMARY A fundamental challenge in neuroscience is in understanding which circuits and cells in the brain contribute to specific behaviors, perceptions, and functions. One class of tools that can help to unveil complex brain circuitry are activity integrators that can record the history of neural activity over a user-specified window of time. Technologies that not only record and map neural activity but enable genetic access to ‘playback’ neural activity can provide an unparalleled understanding of brain circuit structures.

The objective of this project is to evaluate graphenated carbon nanotubes (gCNTs) as lower impedance, smaller electrodes for neurostimulation, using deep brain stimulation (DBS) as a test case, with the long-term goal of developing a new type of neural electrode with lower impedance and smaller size. Lower impedance of the electrode-tissue interface results in lower power consumption, as a smaller voltage is required to achieve the same charge injection. Lower power consumption extends battery life and decreases the size of the batteries and thus of the implanted device.

Project Summary Region-specific enhancement of drug delivery to the brain, without increasing systemic drug dose or actively disrupting the blood-brain barrier, has been sought after for effective pharmacological treatment of various central nervous system disorders. Among different approaches, we propose to enhance the delivery by unbinding the drug from the plasma proteins to increase the local drug concentration that may be transported across the vasculature.

PROJECT SUMMARY Understanding how our brain's 100 billion neurons process information to produce complex feelings, decisions, and behaviors is a daunting task. A single neuron in the human brain may communicate with more than a hundred thousand partners. For each partner, this exchange happens at multiple specialized contact sites called synapses. Genetic studies are now revealing that mutations that alter the formation or activity of synapses are often at the root of neurological conditions ranging from autism spectrum disorder to epilepsy.

Metasurface-Dressed Nanophotonic Neural Interfaces for Multipoint Concurrent Optogenetic Modulation and Calcium Mapping Large-scale recording of neural activity while manipulating arbitrary neurons in freely behaving animals are important for answering many key questions in neuroscience. Optogenetics offers great potential for studying brain function and developing novel therapies for neurological disorders. Taking full advantage of that potential will require stable access for optical stimulation and concurrent monitoring of neural activity.

Project Summary/ Abstract Advancements in microelectrode array (MEA) neural probes have allowed the number of neurons that can be simultaneously recorded by implantable electrodes to roughly double every 7 years since the 1970s, with present state of the art devices allowing for simultaneous recording from thousands of neurons. Unfortunately, continued growth in MEA recording performance faces tremendous challenges from the interrelated constraints on invasiveness of implantation (i.e.