Neuronal mechanisms of selective visual attention - Project Summary/Abstract Visual attention is a universal ability by which an individual’s focus is directed upon a selected visual stimulus in preparation for action. It is (i) a phenomenon that we experience constantly, (ii) a process that has long been studied, and (iii) the target of many neurological disorders such as hemispatial neglect, schizophrenia, and ADHD. Yet, we still do not have a mechanistic understanding of where and how visual selective attention is generated by the brain. Here, I propose to reveal fundamental mechanisms of visual selection by leveraging the rich behavioral repertoire of an invertebrate model that provides connectome-based functional predictions, precise genetic targeting and manipulation at circuit and single-cell levels, and overt orientation behavior toward select objects – an elemental form of attention-like selectivity. I recently showed that a class of visual columnar neurons that send input to the third neuropil of the fly optic lobe detect texture features of visual objects and are imperative for saccadic object tracking behavior. The saccadic tracking pathway resides in the same neuropil as a well-characterized pathway for avoidance responses. Evidence is accumulating that this neuropil is homologous to the optic tectum in vertebrates or superior colliculus in mammals, and thereby can inform general mechanistic principles the neural basis of selective visual attention. In Aim 1 (K99 phase), I will identify the neural components of the object detection and saccadic control, and formalize their computations by means of behavioral, connectomic and opto-physiological studies. I hypothesize that the selection mechanisms underlying this pathway are implemented by inhibitory circuit motifs within and between visual lobes. These studies will further our understanding of simple bottom-up attentional phenomena. Innovative approaches include “read- write” of neural activity with an ‘all-optical’ microscope in flies inside a virtual reality flight simulator. Co-mentors, Dr. Hartenstein and Dr. Huk, will help me dig into connectivity motifs and computational models of neural circuit for orienting behavior. My primary mentor, Dr. Mark Frye, will provide me the necessary guidance to transition to the independent phase. The vibrant and interactive research environment at UCLA represents a key factor for my career development and for the phylogenetic aspect of my research proposal. In Aim 2 (R00), I will bring with me all apparatus necessary to carry out behavioral and physiological investigation of top-down modulation of selective attention by targeting a central structure of the fly brain that coordinates goal-directed actions. I hypothesize that dopamine signaling determines the strength of goal attention, while also modulating the saccade control pathway to reduce distractibility from the goal. These experiments will disclose circuits and algorithms for visual selection-for-action. My long-term career goal as a principal investigator is to pursue how selective visuomotor mechanisms give rise to attentional phenomena.