Project Grant R15EY036226

EXAMINING HOW VISUAL EXPERIENCE MODULATES THE THALAMUS AND VISUOMOTOR RESPONSES. - SUMMARY VISION IS HOW MOST ORGANISMS PERCEIVE AND RESPOND TO THEIR ENVIRONMENT, MAKING THE DEVELOPMENT AND FUNCTION OF THIS SENSORY MODALITY PARAMOUNT. VISUAL EXPERIENCE IS NECESSARY TO REFINE VISUAL PROCESSING, A FORM OF EXPERIENCE-DEPENDENT PLASTICITY. THE MAJORITY OF THIS REFINEMENT OCCURS DURING A BRIEF DEVELOPMENTAL WINDOW KNOWN AS A CRITICAL PERIOD, WHEN VISUAL INPUT CAN PRODUCE EXTENSIVE CHANGES. DURING THE VISUAL CRITICAL PERIOD, THE ABSENCE OF VISUAL EXPERIENCE IS ASSOCIATED WITH AMBLYOPIA (LAZY EYE) IN HUMANS AND IMPAIRED VISUAL ACUITY. THE CIRCUITY UNDERLYING VISUAL TRANSFORMATIONS ARE WELL ESTABLISHED, INCLUDING THE CORTICAL CHANGES IMPOSED BY VISUAL EXPERIENCE. HOWEVER, SUBCORTICAL CIRCUITS (E.G. THE THALAMUS) ALSO EXHIBIT A CRITICAL PERIOD AND VISUAL EXPERIENCE DRIVEN CHANGES. COMPARED TO CORTICAL PLASTICITY THE MECHANISMS INSTRUCTING THALAMIC VISUAL PLASTICITY ARE POORLY UNDERSTOOD. THIS GAP IN KNOWLEDGE MEANS WE HAVE AN INCOMPLETE UNDERSTANDING FOR HOW VISUAL EXPERIENCE REFINES VISUAL CIRCUIT FUNCTION AND PROCESSING. IN ESTABLISHED MODELS, TECHNICAL OBSTACLES EXIST TO ADDRESS THIS GAP, SUCH AS ANATOMY (THALAMUS IS A DEEP BRAIN STRUCTURE), EXTENSIVE CORTICAL FEEDBACK, AND IN VIVO STUDY IS COMPLEX IN DELICATE EARLY STAGE ANIMALS. HERE, WE USE A NOVEL VISUAL CRITICAL PERIOD MODEL IN LARVAL ZEBRAFISH. THE ADVANTAGES TO OUR ZEBRAFISH MODEL ARE THAT VISUAL PLASTICITY CAN BE DEMONSTRATED USING A STRAIGHTFORWARD VISUOMOTOR BEHAVIOR, ABSENCE OF A CORTEX AND THALAMIC FEEDBACK, LARVAE ARE ROBUST AND AMENDABLE TO IN VIVO STUDY, AND THE WHOLE BRAIN IS OPTICALLY ACCESSIBLE -PROVIDING A UNIQUE THALAMUS-CENTRIC VERTEBRATE MODEL FOR VISUAL PLASTICITY. LAST, OUR PRIOR WORK HAS DEMONSTRATED THAT GENETICALLY-DEFINED THALAMIC NEURONS ENCODE VISUAL EXPERIENCE AND DISPLAY ASYMMETRIC PATTERNS OF ACTIVITY THAT CORRELATE WITH BEHAVIORAL PERFORMANCE. THEREFORE, WE HAVE A SYSTEM WHERE VISUAL EXPERIENCE, THALAMIC PHYSIOLOGY, AND CHANGES IN THE PERFORMANCE OF VISUOMOTOR PERFORMANCE CAN BE CORRELATED IN SINGLE ANIMALS. WE WILL USE THIS SYSTEM TO DETERMINE HOW VISUAL EXPERIENCE INSTRUCTS CHANGES TO THALAMIC FUNCTION THROUGH THE ENTIRE VISUAL CRITICAL PERIOD UNTIL BEHAVIORAL ONSET (AIMS 1). CHANGES IN INHIBITORY SIGNALING ARE WELL-ESTABLISHED TO REGULATE THE DURATION OF CORTICAL VISUAL PLASTICITY, YET THE ROLE OF INHIBITION IN THE THALAMUS IS INCOMPLETELY UNDERSTOOD. IN AIM 2-3, WE WILL TAKE ADVANTAGE OF OUR NEW SYSTEM TO DEFINE HOW VISUAL EXPERIENCE MODULATES INHIBITORY INPUT AND DEVELOPMENT IN THE THALAMUS. THE ZEBRAFISH MODEL POSITIONS US TO ADDRESS CURRENT GAPS IN KNOWLEDGE ABOUT THE BASIC MECHANISMS THAT DRIVE CRITICAL PERIOD PLASTICITY IN THE THALAMUS, AND TO DIRECTLY CORRELATE EXPERIENCE WITH BEHAVIORAL OUTPUT. THE LAB HAS AN ESTABLISHED TRACK RECORD OF UNDERGRADUATE TRAINING, PRODUCTIVITY, AND PURSUING FURTHER STEM OPPORTUNITIES INCLUDING TERMINAL BIOMEDICAL DEGREE TRAINING OR BIOMEDICAL RELATED CAREERS. THIS PROPOSAL WILL SUPPORT CONTINUED UNDERGRADUATE INVOLVEMENT IN RESEARCH, WITH AN EMPHASIS ON GAINING HANDS-ON PRACTICAL EXPERIENCES THAT CREATE A FOUNDATION FOR LONG-TERM SUCCESS IN STEM.