Systems Neuroscience

Abstract In many cognitive processes, information is processed in a parallel manner across many brain regions. This is thought to make our cognitive abilities highly tolerant to perturbations or neuron-loss because disrupted processes are compensated by other redundant neurons coding the same information. Yet, it remains poorly understood how interconnected networks of neurons are organized into redundant representations to produce robustness. We recently discovered that persistent activity in mouse frontal cortex during short-term memory is remarkably robust to perturbations.

PROJECT SUMMARY The courtship song of male zebra finches is a classical model for learning complex motor behaviors and shows important parallels to human speech and communication. Male zebra finches learn a song from an adult tutor and then reproduce this song throughout adulthood. The zebra finch model offers outstanding behavioral control that permits the investigation of general principles of the circuit basis of vocal learning and motor control.

Project Summary/Abstract This project will provide a more nuanced and mechanistic model of the role of sleep in memory consolidation, particularly as it pertains to procedural motor skill acquisition in a non-human primate model. Motor skill learning delineated by enhanced speed, automaticity, and accuracy of a correlate strongly with the duration of non-REM (NREM) sleep. Neural reactivations of daytime neural activity preferentially occur during NREM, and disruptions in NREM sleep negatively impacts memory consolidation.

Project Summary/Abstract In sensory decision-making, choices are influenced by non-sensory factors such as motivation, attention, and recent trial history. We seek to incorporate these influences into a drift diffusion model (DDM), by modeling non-sensory variables as deterministic modulators of the starting point or drift rate of sensory evidence accumulation. However, decision-making models are subject to confounds due to the non-stationarity and correlations in long-term behavioral data.

Years of study and theory about the unique role of the hippocampus in storing new memories has led to a general idea that the hippocampus generates a unique output code for every unique experience, that is projected back to the neocortex, where it becomes coupled to attributes of the experience that are widely dispersed over the cortex, thus enabling their coherent retrieval.

PROJECT SUMMARY Understanding information flow in cortical circuits requires understanding both the anatomical connectivity between neurons and the way in which inputs to a neuron are integrated to generate a spiking output. Many techniques are now available to study connectivity across cells and brain areas, but the dendritic integration of these inputs is challenging to observe because we lack access to the complex electrical signals in fine dendrites.

Project Summary: Whether to laugh at a joke or to engage in a lively debate, we flexibly modify our vocalizations based upon social contexts. Such adaptive behavior requires real-time adjustments of motor outputs in response to rapidly changing sensory inputs. How does the brain accomplish this sensorimotor feat? Pioneering studies have characterized the brain areas responsible for sound production in many species (e.g., drosophila, zebra finches, marmosets, mice), but the neural circuits that generate vocal flexibility remain poorly understood.

Abstract The hippocampus has a well-established role in the initial formation and storage of memory. However, little is understood about brain mechanisms that support the re-organization and transfer of memories into longer-term cortical storage. A detailed understanding of hippocampal- to-cortical consolidation is critical to shed light on the regulation of long-term memories, and how they may become too transient (as in Alzheimer’s, Parkinson’s, Traumatic Brain Injury) or too persistent (as in PTSD).

PROJECT SUMMARY Sensory processing is a way to understand the nervous system in action. Behavioral context strongly affects sensory processing. For example, a brief visual stimulus is easier to detect if it appears in a predictable spatial location. This attention to visual space strongly enhances neural and behavioral responses to stimuli in those locations, but the detailed neural mechanisms spanning multiple brain areas remain unknown.

Project Summary/Abstract: Overall The overarching goal of this U19 program is to determine how neural computations across brain regions produce two core cognitive processes, working memory and decision-making, and thus to derive fundamental principles of brain function. This renewal application proposes to pursue powerful new themes that emerged from our previous work and to broaden our scope substantially.