Understanding Circuits

ABSTRACT Resting state networks are a fascinating yet poorly understood phenomenon. Sets of spatially separated regions show correlated slow fluctuations in fMRI BOLD signals, most obvious when subjects are at rest. These networks appear to have clinical imporantance: brain injuries perturb resting state networks, and multiple clinical disorders, including depression, dyslexia and prosopagnosia, are associated with specific resting state network abnormalities.

Attention deficit symptoms are frequently observed in psychiatric disorders, yet finite understanding of the neural circuits mediating attentional behavior has limited pathophysiologic insight. Previous studies in humans and rodent demonstrate that the frontal cortex—especially the anterior cingulate cortex (ACC)— plays a key role in implementing a top-down control of attention. However, the precise neural circuit mechanisms mediating attention remain largely unknown.

Project Summary Understanding the circuit mechanisms that give rise to perception and behavior requires linking neuronal activity to connectivity. This can be accomplished at multiple scales and ideally can be related to further studies using activity manipulations to demonstrate causality. Recent work in the mouse visual system has revealed the contributions of specific cell types to the generation of visual receptive field properties as well as state-dependent changes in the representation of visual information.

Project Summary To survive, organisms must both accurately represent stimuli in the outside world, and use that representation to generate beneficial behavioral actions. Historically, these two processes – the mapping from stimuli to neural responses, and the mapping from neural activity to behavior – have largely been treated separately. Of the two, the former has received the most attention. Often referred to as the “neural coding problem,” its goal is to determine which features of neural activity carry information about external stimuli.

Overview - Abstract Brainstem function is necessary for life-sustaining functions such as breathing and for survival functions, such as foraging for food. Individual motor actions are activated by specific brainstem cranial motor nuclei. The specificity of individual motor actions reflects the participation of motor nuclei in circuits within closed loops between sensors and muscle actuators. However, these loops are also nested and connect to feedback and feedforward pathways, which underlie coordination between orofacial motor actions.

PROJECT SUMMARY/ABSTRACT The mammalian brain has a remarkable ability to store and retrieve information. Detailed memories can be formed after as little as one exposure, and those memories can be retained for decades. This ability is compromised following damage to structures located in the medial temporal lobe, including the hippocampus and the adjacent cortex.

Understanding the cerebral cortex requires data-based theoretical models that can yield in- sight into the circuit mechanisms of cortical computation, and reproduce detailed cortical dynamics across stimuli and brain states. The primary visual cortex (V1) is the best-studied cortical area by both theorists and experimen- talists, yet current models - whether statistical or circuit based – only poorly capture how V1 neurons respond to complex stimuli, such as natural scenes.

Oxytocin is a peptide hormone synthesized and released from the hypothalamus for reproduction and maternal behavior. Recent studies have tagged oxytocin as a “trust” hormone, promising to improve social deficits in various mental disorders, such as autism. Despite the enthusiasm for oxytocin, contradictory results in the efficacy of oxytocin in improving human social behaviors have been reported. Such inconsistency in literature is likely due to our poor understanding of complexity of oxytocin action, which likely varies with behavioral state, experience and brain structures.

Project Summary/Abstract Action initiation and withholding are key parts of everyday behavior, and underlying these is action suppression. This includes (1) suppressing competing actions when selecting one action from alternatives (2) suppressing all responses when presented with conflicting information until a proper decision can be made and (3) suppressing a response when the environment rapidly changes indicating a pre-planned response must be stopped. The literature suggests that these three functions are supported by distinct fronto-basal ganglia (BG) circuits.

ABSTRACT In the course of a day we naturally make multiple shifts in our overall cognitive state and in our aims and intents. We go from sleep to awake, from internal dialogue to external communication, from relative immobility to planned complex movements. The neural activity which distinguishes these different high-level states is unknown and yet is a fundamental aspect to understanding overall cognitive processes. It is also a baseline substrate that is adversely impacted by a wide range of neuropsychiatric diseases.