Circuit Diagrams

ABSTRACT Although behavioral deficits are common in neurological disorders, the genetic pathways and neural circuits underlying behavior are largely unknown. A behavior that is disrupted in numerous disorders including attention deficit disorder, autism spectrum disorders, and schizophrenia is the startle response. Following an intense auditory stimulus, a short latency response occurs wherein rapid muscle activation produces a defensive posture.

Project Summary / Abstract Despite the central importance of neural circuit development to brain function and behavior, we lack the genetic information required to assemble a complete circuit. To address this knowledge gap we propose to develop novel synaptic and neuronal-neighborhood techniques to label a complete circuit in live animals. Using these tools we will genetically dissect a complete neural circuit for the first time, providing fundamental genetic insight into how circuits are built. We will take advantage of C.

PROJECT SUMMARY Blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) is a non-invasive imaging technique that infers the presence of increased brain activity from localized increases in oxygenated hemoglobin. Interpreting BOLD data largely depends on the assumption that neuronal firing and increased blood flow directly correlate across the brain in a process known as neurovascular coupling.

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.