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Project summary Understanding how neural circuits give rise to sensory computation and, ultimately, perception, requires connecting biological features of neural circuits to abstract models of neural computation. In vison, a model of the visual receptive field (RF) describes how a neuron's responses are determined by the visual inputs it encounters. The visual RF can also provide a compact description of a neuron's function, revealing which features of the external environment that neuron is responsible for encoding.

Project Summary A fundamental end-goal of brain-computer interfaces (BCI) is to enable communication in individuals with severe motor paralysis. BCIs decode the neural signals and accomplish the intended goal via an effector, such as a computer cursor or a robotic limb. The BCI user relies on the realtime feedback of the effector's performance to modulate their neural strategy to control the external device. To date, this feedback is predominantly visual.

In dendrites, Ca2+ is critical in determining how neurons respond to incoming excitation. While numerous studies have focused on how dendritic Ca2+ relates to behaviorally-relevant neuronal and circuit activity using correlative observations, there is currently no method to precisely manipulate Ca2+ in neurons in vivo and thus causally test its role in circuit function and behavior. In non-neuronal cells, mitochondria can act as sinks for Ca2+ released from the endoplasmic reticulum (ER) by forming direct contacts with these concentrated intracellular Ca2+ stores.

Project Summary and Abstract A major obstacle to understanding the link between behavior and neuronal activity is the difficulty of electrophysiologically recording the activity of large neuronal populations without limiting visual access. Electrode arrays directly measure electrical signals and offer significantly greater temporal resolution than optical fluorescence techniques, but the resulting obstruction of optical access limits the ability to pair electrode arrays with optogenetic stimulation and calcium imaging.

TOWARD 3D HUMAN BRAIN-LIKE TISSUES FOR TARGETING DYSREGULATED SYNAPSE AND PROTEOSTASIS MECHANISMS IN AUTISM SPECTRUM DISORDER Autism spectrum disorder (ASD) is a neurodevelopmental disease affecting nearly 1/50 children in US with an estimated $268 billion in annual costs. The disease is characterized by significant behavioral abnormalities that are often devastating to the quality of life for these patients. Behavior is directly related to the underlying changes of the central nervous system (CNS) brain tissue.

Project Summary/Abstract The BRAIN initiative has put forth the development of a neuronal cell-type census as the first step towards mapping the structure and components of neuronal circuits.

Project Summary When learning new skills, experience with previously-learned skills can facilitate faster learning by constraining behavioral exploration and shaping, a concept known as “structural learning”3,4. The motor cortex plays an essential role in learning new skills5,6, and its initially variable activity is shaped and consolidated over learning7–10. However, how previous experience modulates exploration and shaping of cortical network activity to facilitate new skill learning is not well understood.

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 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.