Rigourous behavioral paradigms for visuospatial attention

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PROJECT SUMMARY Attention is the remarkable ability of animals to select and preferentially process the most important, or “highest priority”, information in complex environments to guide behavior. This dynamic ability is essential for a range of cognitive functions and adaptive behavior, and its dysfunction is found in diverse psychiatric illnesses including ADHD, autism and schizophrenia. Yet, almost nothing is known about the circuit mechanisms by which the brain implements the selection of the highest priority stimulus at any instant. One key factor that has slowed progress has been the nearly exclusive use of primates for the study of attention: the absence of diverse genetic tools for use in primates has precluded the systematic dissection of cell-type specific contributions and neural computations in cortical and subcortical circuits in service of attention control. Another is that rigorous behavioral paradigms to study attention do not currently exist in any other (genetically tractable) mammalian species. To bridge this gap, we propose an innovate alternate approach: to develop parameterized, primate-like behavioral paradigms for visuospatial attention in the mouse so that the full power of genetic techniques offered by the mouse model can be brought to bear to dissect the neural circuitry underlying attention control. Here, we will develop touchscreen-based tasks in freely behaving mice for studying attention. Specifically, in Aim 1, we will develop three parameterized tasks for studying exogenous (bottom-up) control of spatial attention, namely, a Posner discrimination task, a flanker task, and a Posner-cued selection task. In Aim 2, we will develop two parameterized tasks for studying endogenous (top-down) control of spatial attention, namely, a spatial expectation task and a top-down spatially-cued selection task. Additionally, in Aim 3, we will use head and eye-trackers to develop a closed-loop stimulus presentation system that adjusts, in real time, stimulus locations with respect to the gaze direction of the freely behaving mouse. This will permit consistent retinotopic presentation of stimuli across trials in the above tasks, a requirement for future experiments into the functional signatures as well as causal roles of neural circuits in spatial attention control. Preliminary behavioral data support the feasibility of all three proposed aims. This development, for the first time, of rigorous paradigms for spatial attention in a genetically tractable mammalian model will establish a powerful new platform for future work unraveling neural mechanisms of attention control, as well as of neural information processing pathways that are disrupted in attentional dysfunction.