Research investigating the use of noninvasive electrical stimulation (e.g., transcranial direct current stimulation (tDCS)), for neurologic and psychiatric disorders has provided compelling evidence that such stimulation can modulate behavior and cognition, and even facilitate recovery of function after focal brain injury, with effects typically outlasting the stimulation period.
Abstract Micro-magnetic stimulation (μMS) is an emerging technology with a great promise to revolutionize therapeutic stimulation of human nervous system. Originally developed to stimulation single neurons, μMS uses ultra- conductive neuron-size coils that are capable of carrying current pulses large enough to elicit neural activation by means of magnetic induction.
Abstract Ultrasound (US) neuromodulation has received increased attention in recent years due to its unique ability to non-invasively activate and inhibit neurons. However, the mechanisms of US neuromodulation are not fully understood, and little is known about the optimal parameters that elicit neuromodulation. In this proposal, we will test a recently proposed model of US neuromodulation at the cellular level using patch clamp methods on pyramidal and interneurons, which have differing characteristics that we hypothesize will cause them to respond differently to US.
Project Summary / Abstract In an exciting era of growth in the use of non-invasive brain stimulation, new methods and applications are being disseminated widely with an increasing number of FDA approvals and equipment designed to probe or modulate the brain in fascinating new ways. The problem with this growing enthusiasm is that there are too few studies that have evaluated how tools such as transcranial magnetic stimulation (TMS) induce functional activation throughout a human brain, especially outside of the motor system.
PROJECT SUMMARY - UNIVERSITY OF NORTH CAROLINA-CHAPEL HILL, FROHLICH The alpha oscillation is a thalamo-cortical rhythm (8-12 Hz) that serves important functional roles in cognition and behavior. Transcranial alternating current stimulation (tACS) has been shown to alter cortical alpha oscillations and associated cognitive function in healthy human participants. However, it remains unclear how tACS engages and modulates thalamo-cortical oscillations as a function of stimulation dose (frequency, amplitude, and duration).
Project Summary/Abstract A fundamental goal in neuroscience is to understand how information is processed in neuronal circuits. Ultimately, we would like to understand the relationship between circuit structure and network function. However, the immense complexity of most brain networks has been a significant barrier to progress. Neurons are a primary computational component of networks in the brain, yet we do not have a comprehensive list of their types for even the simplest mammalian neuronal circuit.
Neural circuits encode animal behaviors, and neuroplasticity induces long-lasting changes in neural circuits and animal behaviors. Neural circuits are formed by billions of neurons, which communicate mostly through synapses. Neuroplasticity occurs at the synapse, as neuronal activity modulates synaptic strength through a process known as synaptic plasticity. However, there is no tool to modulate synaptic transmission mimicking synaptic plasticity in vivo. The lack of such a tool makes it difficult to study long-lasting plastic changes in animal behaviors.
Summary/Abstract The ability to control protein function with light provides excellent temporal and spatial resolution for precise investigation in situ, and thus is having significant impact on neuroscience. There are two major barriers imposed by existing optogenetic methods: one being that they cannot be readily applied on any protein of choice, and the other being lack of high specificity and flexibility in site selection for photo-modulation. These limitations significantly restrain the scope, precision, and depth of investigations on neuronal processes.
Project Summary: Our limited ability to genetically access specific cell types within the nervous system constitutes a fundamental impediment in our efforts to probe brain function and intervene therapeutically, particularly in species lacking the well-developed genetic resources available in the mouse. Targeted payload delivery using recombinant viral approaches possesses a number of potential advantages, including anatomical specificity, ease of experimental implementation, and utility in a broad range of mammalian species.
PROJECT SUMMARY Deciphering the complex underpinning of brain structure and function requires a complete understanding of how molecular contacts between cells in the brain are regulated. Currently, there are a lack of tools to measure these intercellular protein-protein interactions (PPIs) with requisite sensitivity, precluding a complete understanding of endogenous regulatory mechanisms. Moreover, as intercellular contacts are guided by thousands of diverse PPIs, it is critical to be able to study multiple interactions simultaneously, which is presently not possible.
