Circuit Diagrams

Abstract The transformation of visual cues into appropriate behavior requires the collaboration of diverse neurons across distant brain areas. A fundamental gap in our knowledge about these visuomotor transformations is understanding how these neurons are functionally connected, shaping neural response dynamics that give rise to behavioral output. This gap is due to the inaccessibility of mammalian model systems, in which simultaneous in vivo observation and manipulations across the brain is impossible as well as a lack of real-time computational frameworks that can capture these dynamics.

Feedback and feedforward gating of sensory signaling through timing in the thalamocortical loop Nearly all sensory experience begins in the periphery, generating sensory signals travelling through the thalamus before reaching neocortex. Despite numerous anatomical and functional investigations into the feedforward projections from thalamus to primary sensory cortex (TC), significantly less is known about the extensive reciprocal corticothalamic (CT) feedback pathway that provides ~40% of input to the thalamus.

Project Summary Neuroscience is entering a new era, where large-scale neural network models can be tested with unprecedent- edly rich measurements of neural activity. This proposal develops a general methodology for linking theory to experiment in this new era and applies the methodology to the problem of primate face recognition.

Project Summary The cerebellum is essential for coordinating motor behavior through rapid adjustments of ongoing movements. To refine movement, the cerebellum processes motor and sensory information, and transmits output that ultimately modulates motor neuron activity to ensure successful execution. The path through which the cerebellum can influence limb movement is through output circuits in the cerebellar nuclei (CN). Yet little is known about how CN circuits are organized and whether discrete pathways are dedicated to specific motor functions for limb control.

Project Summary Animals interact with the world through dynamic, iterative sensory-motor processes that guide their ongoing movement. Odor-guided navigation is the basis for fundamental natural behaviors such as finding food sources, but little is known about the nature of the sensory signals that inform adaptive changes in locomotion. Here we propose to test how spatial information is encoded by distributed activity in the olfactory bulb, and how this information is decoded by higher-order brain areas.

PROJECT SUMMARY/ABSTRACT Higher brain functions include the ability to learn expectations about the world, update those expectations appropriately when given new sensory information, and use those continually updating expectations to guide behavior. How neural circuits implement these flexible information-processing dynamics is not known.

PROJECT SUMMARY Gene regulation at multiple levels is critical for nervous system development and function. A number of mutations leading to global dysregulation of gene expression have been found to disproportionately affect the nervous system, leading to neurodevelopmental and neurodegenerative disorders. Transfer RNAs (tRNAs), which recognize codons and add the appropriate amino acid to growing polypeptides, can dynamically regulate translation.

Project Summary Preeclampsia, a hypertensive disorder of pregnancy, can advance to eclampsia, when the mother displays novel seizures. The mechanisms that cause some preeclampsia patients to advance to eclampsia are unknown. The long-term goals are to identify therapeutic targets to prevent seizures in pregnancy and preeclampsia and to pursue a career as an academic scientist.

PROJECT SUMMARY The cerebellum has long been thought to solely process motor information. Yet, there is a growing literature that points to a role of the cerebellum in processes across multiple domains. Individuals with cerebellar lesions classically have motor deficits but, in some instances, also have problems with executive functioning, emotion processing, language, and social cognition. Multiple psychiatric disorders, including autism spectrum disorders (ASD), have been linked to structural and functional differences in the cerebellum.

Project Summary Primate species frequently use social information to inform their decisions, for instance, to help make inferences about potential threats or rewards in the environment. The Diagnostics and Statistical Manual for Mental Disorders (DSM) has labeled social impairments, including social cognition, as a primary characteristic of many mental health-related disorders, including Autism Spectrum Disorder and Schizophrenia. Therefore, understanding the neurobiology surrounding social cognition and decision-making is of critical importance.