Systems Neuroscience

Despite the fact that visual perception represents such a fundamental aspect of our everyday life, our knowledge of the underlying neural coding of natural stimuli is woefully lacking. One major limitation preventing our understanding of the neural underpinnings of natural vision is the lack of viable methodologies for recording and synchronizing eye movements and incoming visual stimuli from freely-moving monkeys during unrestrained exploratory behavior.

The neuromodulators acetylcholine (ACh) and norepinephrine (NE) are associated with an activated cortical brain state characterized by an increase in the reliability of cortical responses to external stimuli and enhanced performance on behavioral tasks. A key unresolved question is the spatial and temporal scale at which these neuromodulators exert their effects. New methods to directly record the local availability of ACh and NE simultaneously with the activity of neural populations in mice opens up the possibility to answer this question.

ABSTRACT Perceptual decision-making is a fundamental cognitive ability that is vital to healthy, daily functioning and is impaired in many diseases. Although many brain regions are known to be involved, there is no clear brain-wide model of how perceptual decisions are formed and executed and the underlying circuit mechanisms are still largely unknown.

Classical conditioning has been studied in many different animal models, and even in humans. However, the larval zebrafish with its transparent brain offers a unique opportunity to observe large scale changes in synaptic structure that accompany this form of learning. Accordingly, we have developed a novel paradigm for visualizing synaptic changes that occur during classical conditioning in larval zebrafish. Using this paradigm we have observed striking region-specific changes in the distributions of synapses that drive the rewiring of neural circuits that mediate threat responses.

Abstract: Attachment powerfully shapes our development and remains a primary driver of health and well-being in adulthood; disruption of attachments is highly traumatic. While affiliation, defined as general positive social interactions, is shared widely among mammals, attachment, or selective affiliation as a result of a bond, is far rarer and of primary relevance to humans. While affiliation has been studied in a number of contexts, how the neural circuitry that underlies affiliation ultimately contributes to adult attachment remains largely unknown.

Project Summary This proposal explores an emergent computational framework for understanding the neural population codes that support flexible, context-dependent behavior. The current state of the field is based on two competing views. According to the circuits view, fixed behaviors arise from specific anatomically or genetically defined cell populations that serve specific functions. Alternatively, the network computation view instead holds that neural activity provides mixed representations of task variables and can be understood only based on the joint activation of many neurons.

Abstract Central to human and animal cognition is the idea of internal models: an internal repository of knowledge about the structure of the world and its affordances that enables prediction and planning. The existence of such models is fundamental to experience. As we move through the world, the raw instantaneous sensory information that we receive is highly impoverished and dynamic relative to the rich, organized, stable and detailed nature of experience.

ABSTRACT Sleep occupies a third of our lives and sleep-related ailments cost an estimated $100 billion per year, yet the mechanisms governing its regulation remain poorly understood. Despite the substantial progress that has been made in the discovery and understanding of specific sleep-promoting and wake-promoting neuronal and molecular pathways, what is missing is an integrated understanding of how these mechanisms work together in the brain to regulate sleep and wake as whole-brain behavioral states.

Abstract Vision is an active process: we move our head and eyes to explore the sensory world. This is particularly important in situations where a stationary view provides limited information, such as when looking for an object that is occluded or obscured, which is common in complex natural scenes.

Summary Most perceptual, cognitive, and motor functions rely on neuronal activity distributed across multiple networks, often located in different brain areas. In many systems, including the visual system, signaling between areas is bidirectional: lower areas communicate with higher ones via feedforward connections, and higher areas signal to lower areas via feedback. Feedforward pathways are thought to underlie the increasingly sophisticated receptive fields as one ascends the visual hierarchy. The role of feedback signaling in visual processing, in contrast, is poorly understood.