Monitor Neural Activity

A disproportionately large number of mutations resulting in neurodevelopmental and neuropsychiatric disorders target synaptic proteins. Synapse remodeling and loss precede cell death in neurodegenerative disorders, and addictive drugs can alter circuit connectivity. The convergence of so many brain disorders at the synapse indicates that proper synapse structure and efficacy are critical to normal brain function.

Abstract As new recording methods emerge in neuroscience, new statistical techniques are needed to properly relate neural activity to behavior, a given stimulus, or an internal process. Calcium imaging techniques are now widely used in the field of neuroscience due to their ability to easily record many neurons simultaneously. However, many existing statistical techniques and are formulated for spiketime data. In particular, generalized linear mod- els (GLMs), are developed under the assumption that neural data is in the form of individual spike times.

Learned associations between environmental stimuli and organism-effecting outcomes guide adaptive behavior. When healthy, this process results in increased rewards and decreased harm. Indicative of its foundational role in shaping behavior, associative learning dysfunction is comorbid in a host of neuropsychological pathologies including depression, addiction, anxiety disorders, and post-traumatic stress disorder.

PROJECT SUMMARY How information is transformed as it propagates through a neural circuit remains an outstanding question of modern neuroscience. Answering this question for a given circuit requires knowledge of: 1) the information being transformed, 2) activity in pre- and postsynaptic populations, and 3) connectivity between pre- and postsynaptic populations. The tremendous complexity of neural circuits has made such investigation exceedingly difficult, with success limited to small local circuits or across gross brain regions.

Project Summary The goal of the proposed project is to test in macaques a technique for non-invasive, safe, reversible, modulation of neuronal activity in small targeted regions of the primate brain. We have developed and tested in macaques a technique for transiently opening the blood-brain barrier (BBB) in targeted brain regions without causing any damage, using a clinically available focused ultrasound device in conjunction with circulating microbubbles.

PROJECT SUMMARY/ABSTRACT Fast microscopy techniques, coupled with recent advances in tissue clearing, are now able to efficiently produce cellular-resolution images of intact brain samples. These technologies have generated three- dimensional (3D) images of entire intact brains from model organisms and large sections of human brain samples, enabling mapping of neuronal circuits from synapse to systems levels. Going forward, it will be essential to share data across laboratories to replicate findings, perform cross-study analyses, and develop robust new analysis tools.

PROJECT SUMMARY Technology for recording from the brain is developing at a breakneck pace. But the digital integration of data acquired from different recording technologies is an impediment to the rapid adoption of these technologies across labs, and also makes analysis by interested 3rd parties, such as theorists, difficult. This lack of integration is a major barrier to scientific inquiry, as labs cannot easily analyze each other's data.

ABSTRACT Despite the increasing use of transcranial magnetic stimulation (TMS) in both research and clinical practice, the field nonetheless lacks a theoretical framework to predict the impact of TMS on circuits. In this application, we propose to test the over-arching hypothesis that brain responses to TMS are governed by both the network control properties of the stimulation site and the functional context of the network during stimulation.

Project Summary/Abstract Brain function is produced by the coordinated activity of multiple neuronal types that are widely distributed across many brain regions. Neuronal signals are acquired using extra- and intracellular recordings, and increasingly optical imaging, during sensory, motor, and cognitive tasks. Neurophysiology research generates large, complex, heterogeneous datasets at terabyte scale. The data size and complexity is expected to continue to grow with the increasing sophistication of experimental apparatus.

Project Abstract Completely noninvasive neuromodulation using focused ultrasound (FUS) offers the promise of precisely stimulating specific targets deep in the brain, at power levels commonly used for diagnostic imaging studies. Having a working mouse model to study neuromodulation with ultrasound is a critical need. The mouse model has a much wider array of immunohistochemical staining antibodies and known genetic markers to answer basic science questions than do larger animals.