Systems Neuroscience

Sensory processing requires the interaction between external inputs and an internal brain state. Pain is a unique sensory experience that is triggered by external signals, but is also strongly shaped by internal cognitive and emotional variables. At the circuit level, there is not a single primary pain cortex; instead, a distributed network of cortical areas process and regulate pain. For example, the primary somatosensory cortex (S1) is known to process stimulus-evoked information, such as location and timing.

Project Summary [30 lines max] Timing is critical to neural processing. Nowhere is that clearer than in visual motion detection. To detect motion, neurons transmit visual information with different latencies, or delays, allowing the circuit to compare visual scenes over time. When comparisons over time are combined with comparisons over space, the circuit can compute direction-selective signals, which are larger for motion in one direction than in the opposite direction. These signals in turn guide a wide range of behaviors, from navigation and predator avoidance to mating.

Project Summary Here, we propose to thoroughly characterize the origins of pairwise correlations in cortex using a synergistic mix of experimental methodologies, behavior, and computation in mice and macaques. We will elucidate the mechanistic underpinnings of normalization and test our hypothesis that changes in cortical pairwise correlations and other signature arise from ongoing cortical computations.

We propose a circuit-level principal underlying how brains acquire 'episodic' memories and reprocess them into compact, efficient 'schemas': The attributes or 'contents' of experience are represented primarily in the deeper layers of neocortex (NC), whereas the superficial layers are dedicated to encoding the contexts in which the attributes occur.

Project Summary A fundamental gap in our knowledge of the nervous system is understanding how variations in wiring and connectivity of neuronal circuits relate to variability in neural computations and behavior. This gap has arisen because anatomical connectivity and function are typically studied separately. Here, we will assemble a team of researchers with complementary skills to tackle this problem.

Project Summary / Abstract This grant focuses on how very recent experiences––over the past few seconds to minutes––allow brains to update expectations about the world and then use these expectations to guide behavior. The ability to flexibly adjust one's course of action in this manner is a hallmark of adaptive human behavior. At the neural level, relevant cellular-activity correlates have been described in non-human primates and other vertebrate model systems.

The ability to generate complex motor behaviors by assembling sequences of movements is essential for purposeful actions and survival. Defects in the brain regions thought to drive such movement selection can lead to behaviors becoming abnormally repetitive (e.g. autism spectrum disorder). Yet, the neural circuit architectures that underlie this fundamental function of the nervous system remain poorly understood. A central model of a neural circuit architecture that can account for how movements are assembled into sequences has emerged from studies across multiple species.

Project summary The plight of the neuroscientist trying to understand the brain using linear analysis methods is akin to studying the makeup of the ocean using the bits you find with a metal detector. Everything we know about the neural basis of decision making, from biology to computation to behavior, makes it clear that the relationship between neurons and behavior is profoundly nonlinear. However, for good mathematical reasons, our attempts to understand that relationship typically rely only on linear measures.

PROJECT SUMMARY How does the brain balance the need to preserve prior knowledge with the necessity to continuously learn new information? The tradeoff between stability and plasticity is inherent in both biological and artificial learning systems constrained by finite resources and capacity. The hippocampus is a brain region critical for memory formation and spatial learning, which can provide a powerful experimental system for characterizing this tradeoff.

Project summary Vision plays a key role in our ability to navigate through the environment, from identifying landmarks and obstacles to determining location and heading. While studies of visual cortex have provided an understanding of properties such as orientation selectivity and object recognition, much less is known about how cortical circuitry extracts and processes features from the visual scene to support navigation. In particular, there are two challenges.