Theory & Data Analysis Tools

Cortical circuits perform computations to generate appropriate behaviors based upon diverse sensory inputs. These computations are central to an animal maintaining its health and long- term survival. An example of this type of computation are perceptual decision-making tasks where an animal must weigh sensory evidence to choose a behavior which will elicit a reward. The classical circuit models of decision-making focus solely on the effects of recurrent excitation, treating inhibitory neurons as agnostic facilitators of competition between excitatory subpopulations.

Project Summary/Abstract Astrocytes comprise up to half of mammalian brain cells. Accumulating evidence from multiple brain circuits suggests that astrocytes, through their intracellular Ca2+ signaling, regulate and modulate neuronal activity on single-cell and network-wide levels and on a broad range of timescales—from milliseconds to days and weeks. Altered astrocyte Ca2+ signaling has also been implicated in a variety of brain disorders, including Huntington’s Disease, Alzheimer’s Disease, obsessive-compulsive disorder, stroke, and epilepsy.

Project Summary A fundamentally important motor pattern for terrestrial animals is walking. Walking requires precise control of large numbers of motor neurons. In order to simplify the task of motor control, it has been proposed that motor neurons controlling similar movements are organized in a recruitment hierarchy such that motor neurons are progressively recruited in greater numbers as force requirements increase.

Project Summary/Abstract In a world filled with sensory information, the ability to filter out repetitive or redundant stimuli while still maintaining the ability to detect change in the environment is critical to biological success. Studies have characterized reduced cortical responses to repetitive stimuli (adaptation) and augmented cortical responses to stimuli that differ from these expected regularities (novelty detection); however, the cortical circuits that enable flexibly encoding stimuli based on the context in which they are experienced remain unknown.

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.