Selective visuospatial attention in freely moving mice

Selective spatial attention, the ability to prioritize information from the most important spatial location to a behaving animal at any instant, is critical for guiding behavior in complex environments. The dysfunction of attention is associated with diverse psychiatric illnesses including ADHD and schizophrenia. A rich body of work into selective visuospatial attention in humans and non-human primates has provided insights into the consequences of attention to behavior and neural processing, and has identified the involvement of frontoparietal and midbrain networks in attention control. However, the neural circuit mechanisms underlying the control of selective attention remain largely open questions. A major hurdle to progress on this front has been the lack of genetically-tractable animal model systems that are essential to bring to bear cutting-edge technologies for cell-type specific and projection specific interrogation of neural circuits. In parallel, whereas selective attention has been studied nearly exclusively in head-fixed animals, because it operates in nature in animals engaging freely with the world, the study of its neural underpinnings can benefit greatly from investigations in unrestrained animals in a behavioral state resembling natural conditions: with intact vestibular feedback cues as well as coordinated body movements. In response to these needs, I have developed, for the first time, two human-inspired behavioral tasks for the study of endogenous as well as exogenous control of visuospatial attention in freely moving mice. First, I examine in detail, behavioral signatures of mice in a visual orientation discrimination task, which forms the foundation of our attention tasks. These results provide insights into fundamental limits in mouse visual behavior, such as the shortest duration of visual stimulus exposure need by mice to make effective judgements, the longest stimulus duration that continues to provide additional performance benefits, and the duration of their visual working memory. Next, using the discrimination task as the basis, I develop mouse versions of the spatial probability task and the flanker task of attention. In the spatial probability task, I find enhanced response accuracy, perceptual discriminability, and rates of sensory evidence accumulation at the location with higher probability of target occurrence, and opposite effects at the lower probability location. In the absence of systematic differences in sensory input, motor biases, and trial structure, these results demonstrate endogenous expectation-driven shifts of spatial attention. In the flanker task, I find that a second, ‘flanker’ stimulus presented with the target, but with incongruent information, caused switch-like decrements in response accuracy and perceptual discriminability as a function of flanker contrast, as well as a reduced rate of evidence accumulation. These results demonstrate exogenous capture of spatial attention. I conclude with several promising directions of future work into the dissection of circuit mechanisms of selective attention control. The innovation of behavioral tasks for selective visuospatial attention in unrestrained mice, together with estimates of the limits related to their visual discrimination behavior, sets the stage for research into the neural circuit basis of this critical executive function in an unprecedented way