Theory & Data Analysis Tools

Project Summary/Abstract This proposal is being submitted to support the transition of Dr. Dominguez-Lopez from mentored trainee to an independent investigator in the neurobiology of drug addiction, specifically studying the dopamine microcircuits controlling drug-seeking behavior. Dr. Dominguez-Lopez works under the mentorship of Dr. Michael Beckstead at the Oklahoma Medical Research Foundation (OMRF) investigating the role of dopamine neurotransmission in the ventral tegmental area (VTA) in methamphetamine (METH) self- administration behavior. Dr.

Project Summary My long-termcareer goal is to establish a research laboratory that dissects functional microcircuits supporting flexible social behavior in typical and perturbed development. The lab will integrate state-of-the-art techniques into a large toolkit of convergent methodologies to assess how neural networks exhibit plasticity to support adaptive behavior in early life. To effectively lead this future research team, I require additional professional development and training in techniques for measuring and manipulating neural function in behaving infants.

Proprioception is critical for effective motor control: dysfunctions of the proprioceptive system can impair balance, motor coordination, and motor learning. However, despite its importance, little is known about the initial stages of proprioceptive processing in any animal, nor how this information is modulated by behavioral state. I propose studying proprioception in the fly, D. melanogaster, whose proprioceptive system is more experimentally accessible than that of vertebrates, but still analogous in its organization and function.

Project Summary Astrocytes are evolutionarily conserved and constitute a substantial proportion of the cells in the brain, yet our understanding of their identities and functions is far less comprehensive than for neurons. Astrocytes are thought to be important for regulating the formation and function of neuronal circuits, playing multiple roles in neurotransmitter reuptake, ionic buffering, metabolic support, and plasticity. Evidence from both mammals and Drosophila has also indicated that astrocytes are diverse in both function and morphology.

Project Summary The visual system must constantly extract behaviorally relevant stimulus information from an abundance of irrelevant inputs from the environment, using cognitive phenomena such as attention and learning to guide this continuously adapting process. Understanding the mechanisms by which task-relevant information is extracted from the high-dimensional activity of neuronal populations will be vital to understanding the complex etiology of many neurological diseases, such as disorders of attention.

Project Summary – Restoring Sight to the Blind: Neural Imaging with Retinal Prostheses Retinal prostheses restore sight to the blind by electrically stimulating still viable cells in the retina. These devices consist of a microstimulator array attached to the retina that is driven by video input from a glasses-mounted camera. Retinal prostheses have been shown to restore basic visual functions such as the recognition of shapes and rudimentary navigation.

Project Summary Social deficits are common in psychiatric disorders and available treatments are limited. Our lack of basic knowledge on how the brain controls social behaviors makes it challenging to develop therapeutics for social deficits. For numerous animal species, social rank dictates many aspects of behavior, such as access to resources and resilience to stress. Individuals with higher social rank typically win more often during social conflicts (e.g. food competition) and show more agonistic behaviors; collectivity referred to as dominance behaviors.

PROJECT SUMMARY/ABSTRACT Determining the mechanisms by which the human brain generates cognition, perception, and emotion hinges upon quantifying the relationships between coordinated brain activity and behavior. NIH-funded brain mapping initiatives such as the Human Connectome Project (HCP) and the Adolescent Cognitive and Behavioral Development (ABCD) study, have accelerated the production of large brain connectivity (i.e. connectome) and behavioral datasets.

 DESCRIPTION (provided by applicant): Neurological disorders affect many millions of people in the United States and throughout the world. Recent advances enable the development of adaptive neurotechnologies, powerful new technologies that interact with the nervous system to promote functional recovery. These technologies are inherently multidisciplinary: they involve neuroscience, biomedical engineering, electrical and computer science, signal processing, and clinical, ethical, and commercial domains. Very few people can function effectively across all these fields.