Research Projects

High-throughput Physiological Micro-connectivity Mapping in Vivo

PROJECT SUMMARY Mapping the synaptic connectivity of brain circuits is essential for obtaining a mechanistic understanding of the neural basis of behavior, learning, and cognition. While anatomical approaches can reveal the physical architecture of neural circuits, only a functional approach can reveal the strength and dynamics of each synapse in a network. These parameters are crucial for building any type of quantitative and explanatory model for how neural circuits compute, encode, and store information.

Developing new tools for high throughput analysis of microcircuits and synapse ultrastructure using tagged vesicular transporters and deep learning.

PROJECT SUMMARY Synaptic dysfunction is a common feature of neuropsychiatric disease. For example, a hallmark of age-related neurodegenerative diseases such as Alzheimer’s and Parkinson’s is synaptic fibrilization and aggregation of key proteins that participate in synapse and cell loss. Maladaptive plastic changes in synapse structure and function underlie key aspects of behavioral and mood disorders ranging from addiction to depression, as well as neurodevelopmental diseases like schizophrenia and autism.

Axonal connectomics: dense mapping of projection patterns between cortical areas

Project Summary/Abstract Connectomics is a new field, created with the goal of densely or completely mapping the connections in the brain. Because this goal is at present only achievable for small organisms, connectomics has taken on two forms in the study of larger brains. Macroscale connectomics is used to describe the connections between brain areas, which in experimental animals is achieved with tracers, while humans it is typically pursued at a very coarse scale with diffusion imaging, a form of MRI.

Reversing Synchronized Brain Circuits with Targeted Auditory-Somatosensory Stimulation to Treat Phantom Percepts

Abstract The dorsal cochlear nucleus (DCN) integrates auditory and somatosensory information through circuitry that modulates activity of the principal output neurons of the circuit, the fusiform cells. Fusiform cells receive somatosensory information via synapses on their apical dendrites and acoustic information via their basal dendrites. When somatosensory activation is combined with sound, the circuit can be strengthened or weakened depending on the order of the bimodal stimuli. This process is called stimulus timing dependent plasticity.

Impact of Timing, Targeting, and Brain State on rTMS of Human and Non-Human Primates

Non-invasive methods for stimulating the human brain show great promise for safe, effective treatments of psychiatric and motor disorders, and are in widespread use for basic research on human behavior and cognition. One such method, transcranial magnetic stimulation (TMS), is the application of time-varying magnetic fields above the scalp that induce transient electrical fields in the brain. TMS clearly stimulates the brain and affects behavior, but we do not know why it works; its effects on neural activity within brain regions and networks are not understood at a biological level.

Transcranial magnetic stimulation with enhanced focality and depth (fdTMS)

This project will develop transcranial magnetic stimulation coils with improved focality and depth (fdTMS). TMS is a technique for noninvasive brain stimulation using strong, brief magnetic pulses. TMS is widely used in the neurosciences as a tool for probing brain function and connectivity. Presently, TMS is FDA-approved for the treatment of depression and for pre-surgical cortical mapping, and is under study for other psychiatric and neurological disorders.

The impact of cerebellar tDCS in local and downstream brain circuits: how much is neuralactivity modulated in the resting state and during sensorimotor processing?

PROJECT SUMMARY Non-invasive stimulation of the cerebellum holds great promise for investigating brain function, and for diagnosing and treating a variety of brain disorders. Given the classical role of the cerebellum in motor control, it is not surprising that many studies have reported that cerebellar transcranial direct current stimulation (CB- tDCS) can be used to enhance motor function and mitigate the symptoms of ataxia, dystonia and essential tremor.

Using fMRI to Measure the Neural-level Signals Underlying Population-level Responses

Project Summary: The goal of this proposal is to advance our ability to accurately infer the properties of neu- ral-level responses from the more coarse-grained information obtained with non-invasive imaging in humans. To achieve this goal, the project will capitalize on feature-selective cortical responses. For example, many neu- rons in visual cortex exhibit a tuning function such as a response profile in which firing rate is greatest for one orientation of a line, and falls off for orientations progressively less similar to that orientation.

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