Mechanisms of Bottom-up and Top-down Control of Spatial Attention

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DESCRIPTION (provided by applicant): How does competitive stimulus selection work, at the level of cells and circuits? In primates, stimulus selection is controlled in two fundamentally different ways: bottom-up and top- down. We have developed automated behavioral tasks that demonstrate both kinds of control of stimulus selection in chickens. In primates, a midbrain network is essential to competitive selection. What are the circuits that cause the selection of one stimulus and the suppression of all others, and how do they work? The midbrain network is highly conserved across vertebrate species, from fish to mammals, and it is most differentiated in birds. The highly differentiated avian network provides the opportunity to test the effects of inactivating specific, specialized circuits on stimulus selection behavior. Preliminary studies in birds indicate that a specific cholinergic circuit contributes to the bottom-up control of stimulus selection, and that a specific GABAergic circuit participates in the suppression of competing stimuli. In Aims #1 and 2 we analyze quantitatively the properties of bottom-up and top-down control of competitive stimulus selection in chickens. In Aim #3, we test the respective contributions of the specialized cholinergic and GABAergic circuits to bottom-up and top-down control of stimulus selection. Understanding the role of these circuits in selection behavior will greatly advance our understanding of how the midbrain network performs these essential functions. The results will lay the foundation for future recording, inactivation, microstimulation, and optogenetic studies into mechanisms of attention control, how to identify dysfunction of specific attention-related circuits, and how to restore function to damaged networks. PUBLIC HEALTH RELEVANCE: Dysfunctional control of stimulus selection for attention is a core component of many, prevalent neurological diseases, including Schizophrenia and ADHD, for which no cures are currently available. We will test the hypothesis that fundamental characteristics of competitive stimulus selection are shared between chickens and humans, and we will test the roles of specific neural circuits in attention-related behaviors. The unique advantages of this species are its well characterized and highly differentiated midbrain network and its availability, trainability, availability, and robust selection behavior. These unique advantages will vastly accelerate the discovery of cellular and circuit mechanisms of stimulus selection, and the discovery of therapeutic remedies this knowledge will provide.