Theory & Data Analysis Tools

PROJECT SUMMARY/ABSTRACT New technologies that modulate brain function have tremendous potential for alleviating the persistent burden of depression and other neuropsychiatric disorders, but also raise challenging ethical and societal questions regarding self-ownership and control over our thoughts, emotions and actions. For these reasons, the President’s Bioethics Commission and other experts have called for the integration of ethics and neuroscience from the earliest stages of research.

Project Summary/Abstract Circuit mechanisms underlying evidence accumulation during decision-making Behavior across many types of decision-making is well described by the gradual accumulation of evidence toward one of multiple alternatives. Neuronal correlates of the accumulation of evidence during perceptual decision-making have been observed in many areas in the brain. Recent work in a rat auditory evidence accumulation task has identified a causal role for a number of brain structures, including the frontal cortex, basal ganglia, and the superior colliculus.

PROJECT SUMMARY Research participants face complex decisions about the surgical removal of implanted devices upon exiting clinical trials of implanted neurotechnology. Ethical safeguards are needed to ensure consent practices and exit procedures respect the bodily integrity of research participants while minimizing risks associated with exposure to novel neurotechnologies. The current research will first characterize and evaluate existing safeguards through a review of regulations and research practices related to exit from neurotechnology research protocols.

Project Summary Chronic sleep disturbance affects 10-20% of the population in the developed world, representing a substantial public health problem. Given the ubiquitous nature of sleep across the animal kingdom, intense investigation is underway into the biological functions of sleep. A primary hypothesis is that sleep facilitates memory consolidation following learning, as sleep restriction or fragmentation impairs memory performance across species. The circuitry coupling sleep and memory remains undefined.

7. Project Summary/Abstract Opioid receptors (ORs), consisting of -, -, and -ORs, are neuropeptide receptors that are broadly involved in regulating analgesia, mood, reward, and motor coordination. Opioid signaling is correspondingly implicated in a variety of behavioral disorders, including depression, drug addiction, stress, and dyskinesia. Understanding how OR circuit activity influences behavior is therefore critical to developing better treatments for disorders such as depression and addiction.

Project Summary Dopamine (DA) is a powerful neuromodulator that facilitates memory formation and underlies reward-related behaviors by regulating synaptic plasticity. Microdialysis and voltammetry are commonly used to measure extracellular concentrations of neuromodulators in vivo, but these techniques suffer from poor temporal resolution and neurotransmitter specificity, respectively.

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.