Circuit Diagrams

PROJECT SUMMARY ABSTRACT The lateral cerebellum (Crus I/II) interacts with two dissociable large-scale brain networks — the executive control (ECN) and default mode networks (DMN), which support distinct cognitive functions (e.g., prediction versus episodic memory, respectively). The proposed research aims to identify noninvasive brain stimulation parameters that cause this area of the cerebellum to interact more heavily with either network, thereby biasing lateral cerebellar participation in network-specific cognitive functions critical to adult humans.

Project Summary The goal of this proposal is to develop a widely adoptable, high-throughput, functional connectomics platform to semi-automatically reconstruct and analyze the synaptic connectivity of functionally characterized neuronal microcircuits. We will develop this pipeline in the context of understanding neural microcircuits that control walking, using the Drosophila ventral nerve cord (VNC) as a model system.

Project Summary/Abstract We have recently published a 3D electron microscopy volume of the whole fruit fly brain. However mapping of synaptic `wiring diagrams' or connectomes of neuronal circuits from this volume is currently completely manual and therefore slow. Our long-term goal is to increase understanding of how circuits process and transform information, both by accelerating connectomics mapping, and increasing the power and accessibility of analysis tools.

PROJECT SUMMARY Mapping the synaptic connectivity of brain circuits is essential for obtaining a mechanistic understanding of the neural basis of behavior, learning, and cognition. While anatomical approaches can reveal the physical architecture of neural circuits, only a functional approach can reveal the strength and dynamics of each synapse in a network. These parameters are crucial for building any type of quantitative and explanatory model for how neural circuits compute, encode, and store information.

PROJECT SUMMARY Synaptic dysfunction is a common feature of neuropsychiatric disease. For example, a hallmark of age-related neurodegenerative diseases such as Alzheimer’s and Parkinson’s is synaptic fibrilization and aggregation of key proteins that participate in synapse and cell loss. Maladaptive plastic changes in synapse structure and function underlie key aspects of behavioral and mood disorders ranging from addiction to depression, as well as neurodevelopmental diseases like schizophrenia and autism.

Project Summary/Abstract Connectomics is a new field, created with the goal of densely or completely mapping the connections in the brain. Because this goal is at present only achievable for small organisms, connectomics has taken on two forms in the study of larger brains. Macroscale connectomics is used to describe the connections between brain areas, which in experimental animals is achieved with tracers, while humans it is typically pursued at a very coarse scale with diffusion imaging, a form of MRI.

Project Summary There is no dedicated sensory organ for time, and yet our brains are able to use time to anticipate the environment and adapt. The process of interval timing on a seconds to minutes scale is evolutionarily widespread and is central to critical cognitive tasks and behaviors, including how to optimally find food. Despite the importance of this ability, there is no known neural mechanism for interval timing on this scale in any organism.

Project Summary Integration of sensory information with motor commands allows movement to be adaptable. For example, many survival-critical orofacial behaviors (chewing, drinking, breathing, etc.) involve updating movement trajectories based on interaction with objects (e.g. matching chewing patterns to food material properties). Proprioceptors, which are sensory afferents that provide information about body position, likely play critical roles in this process.

Project Summary / Abstract Ascertaining the neural basis of behavior has been a cornerstone goal since the conception of neurobiology. While activity recording and loss-of-function studies have shed light on brain regions involved and necessary for the expression of certain behaviors, they are unable to determine the information each circuit is responsible for encoding.

PROJECT SUMMARY/ABSTRACT The basal ganglia are a group of deep brain nuclei that play a central role in motivating, selecting, and learning actions. The largest of these nuclei, the striatum, serves as the principal input, receiving widespread convergent excitatory innervation from cortex and thalamus, as well as dopamine (DA) inputs from the midbrain.