Project Summary Individuals decide between alternatives based on their perceived value of the reward associated with each option. In humans, this value-based decision-making behavior varies by sex and across the menstrual cycle. However, it is not understood how endogenous sex hormones influence the neural dynamics that underlie decision-making.
ABSTRACT Investigating how neural circuits mediate natural behavior is a critical to our understanding of the brain. Exploratory behaviors are necessary for rodent survival in the natural world and ubiquitous in freely-moving rodent experiments. One neural circuit that may mediate natural exploratory behaviors are the projections from prelimbic cortex (PL, part of rodent prefrontal cortex) to ventral tegmental area (VTA). Stimulation of PL-VTA projections causes increased velocity but is not rewarding, despite the well-known rewarding effect of direct stimulation of VTA-dopamine neurons.
PROJECT SUMMARY/ABSTRACT Animals exhibit a remarkable array of creative, adaptive, and flexible behaviors. Birds and primates repurpose new materials to build nests and tools; rats efficiently construct navigational shortcuts, and humans generalize knowledge of one language to efficiently speak another. This ability to dynamically create novel behavior “in a single trial” depends on compositional planning, or mental processes that generate strategies by recombining previously learned behavioral components.
Project Summary Circadian rhythms are necessary to coordinate the timing of key behavioral and physiological processes in mammals [1-3]. However, while our understanding of the function of circadian clock genes in embryonic development is rapidly advancing [4-6], the molecular mechanisms through which these rhythms emerge during stem cell differentiation remain elusive [7]. Recently, signaling by reactive oxygen species (redox signaling) has emerged as an essential link between cellular metabolism and circadian rhythms in adult function [8, 9].
The most widespread tool for measuring brain activity noninvasively in humans is functional magnetic resonance imaging (fMRI), which typically tracks changes in blood flow and oxygenation using the blood-oxygenation-level- dependent (BOLD) signal. Although BOLD is an indirect measure of neural firing, it has been shown to be a faithful measure of brain activation, yet the details of brain vascular anatomy and physiology are known to influence all fMRI signals including BOLD.
Project Summary/Abstract Selecting future actions based on previous experiences is key to an animal's survival. This process, known as action selection, depends on the proper function of cortical and subcortical basal ganglia circuits. Despite the importance of these regions for using previous experiences to inform upcoming motor choices, we do not understand the precise mechanisms by which these regions work together and the activity patterns they use to select actions.
Project Summary/Abstract Sex hormones are critical for sexual differentiation of the brain and body and diverse physiological processes across our lifespan. In particular, sex hormone signaling in the brain has been implicated in mood and emotional well-being, cognitive function, sexual orientation, gender identity, and libido. Many neurological and psychiatric conditions, including depression and anxiety, PTSD, Alzheimer’s disease, multiple sclerosis, Parkinson’s disease, ADHD, schizophrenia, and autism manifest with sex-skewed ratios or outcomes for poorly understood reasons.
Project Summary We propose to develop and test a novel noninvasive neuromodulation technique integrating transcranial focused ultrasound (tFUS) with electrophysiological source imaging (ESI) to allow real-time evidence-based neuromodulation with spatio-temporal precision for brain research and managing brain conditions.
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.
PROJECT SUMMARY . In psychiatry, we are limited by the mismatch between the diverse heterogeneity of the brain and the tools we have to treat it. We know from anatomic, cortical mapping, and imaging studies that every several millimeters of the brain is constituted, connected, and functions in a unique and significantly different manner.
