Not listed THE MEDIATION OF OCULOMOTOR LEARNING BY THE CEREBELLAR CORTEX - PROJECT SUMMARY/ABSTRACT POOR CONTROL OF EYE MOVEMENTS BY THE BRAIN CAN LEAD TO VISION LOSS. HOWEVER, THE NEURAL MECHANISMS THAT CORRECT EYE MOVEMENTS IN RESPONSE TO VISUAL ERRORS (OCULOMOTOR LEARNING) REMAIN INCOMPLETELY UNDERSTOOD. SACCADES, WHICH ARE RAPID EYE MOVEMENTS THAT DIRECT THE FOVEA TO TARGETS, REQUIRE PRECISE ADAPTIVE CONTROL TO ENSURE VISUAL ACCURACY WITHOUT REAL-TIME VISUAL FEEDBACK. ELUCIDATING THIS ADAPTIVE OCULOMOTOR CONTROL IS CRITICAL, AS EYE MOVEMENT DISORDERS WITH CEREBELLAR INVOLVEMENT OFTEN IMPAIR THIS PROCESS AND COMPROMISE ACTIVE VISION. ADAPTIVE CONTROL OF SACCADES DEPENDS ON THE OCULOMOTOR VERMIS (OMV) OF THE CEREBELLUM, WHICH IS ORGANIZED INTO MICROCIRCUITS COMPOSED OF MOLECULAR LAYER INTERNEURONS (MLIS), PURKINJE CELLS (P-CELLS), AND CLIMBING FIBERS. TO DATE, LITTLE IS KNOWN ABOUT THE ROLES OF DISTINCT MLI SUBTYPES AND THEIR INTERACTIONS WITH P-CELLS DURING OCULOMOTOR LEARNING. I HYPOTHESIZE THAT (I) MLIS EXHIBIT PLASTIC CHANGES THAT ARE DISTINCT FROM THOSE OF P-CELLS, AND (II) VISUAL ERROR FEEDBACK FROM CLIMBING FIBERS NOT ONLY INSTRUCTS P-CELLS BUT ALSO MLIS. OVERALL, THE CENTRAL GOALS OF THIS PROPOSAL ARE TO DETERMINE HOW PLASTICITY WITHIN MLIS MODULATES P-CELL OUTPUT TO FACILITATE OCULOMOTOR LEARNING, AND TO DEFINE HOW VISUAL ERROR SIGNALS ARE DISTRIBUTED ACROSS CEREBELLAR MICROCIRCUITS. THIS PROJECT LEVERAGES A LEARNING PARADIGM OF SACCADE ADAPTATION AND HIGH-DENSITY NEURAL RECORDINGS FROM THE OMV IN THE COMMON MARMOSET, A SMALL PRIMATE MODEL UNIQUELY SUITED FOR STUDYING OCULOMOTOR CONTROL AT CELLULAR RESOLUTION. BY UNDERSTANDING HOW CEREBELLAR NEURONS RESPOND TO TYPES OF VISUAL ERRORS AND BEHAVIORAL CONTEXTS, THIS PROJECT WILL DEFINE HOW CEREBELLAR MICROCIRCUITS ADAPT EYE MOVEMENTS. TO INVESTIGATE MY HYPOTHESIS, I PROPOSE THE FOLLOWING AIMS: AIM 1: IDENTIFY THE ROLES OF MLI1S AND MLI2S IN SHAPING P-CELL OUTPUT DURING CEREBELLAR LEARNING. AIM 2: DEFINE THE SPATIOTEMPORAL DYNAMICS OF CLIMBING FIBER INPUT TO P-CELLS AND MLIS DURING VISUAL ERRORS. TOGETHER, THESE STUDIES WILL ENHANCE THE UNDERSTANDING OF HOW ERROR SIGNALS RESHAPE NEURAL CIRCUITS TO SUPPORT PRECISE OCULOMOTOR BEHAVIOR. BY REVEALING FUNDAMENTAL CELL TYPE-SPECIFIC AND CIRCUIT-LEVEL CONTRIBUTIONS TO THE PLASTICITY THAT UNDERLIES ADAPTIVE EYE MOVEMENTS, THIS WORK WILL LAY THE FOUNDATION FOR LEVERAGING ADAPTIVE CEREBELLAR FUNCTION IN TREATMENT APPROACHES FOR PROTECTING AND RESTORING VISION. $55.1k 6/18/26 Not listed THE MEDIATION OF OCULOMOTOR LEARNING BY THE CEREBELLAR CORTEX - PROJECT SUMMARY/ABSTRACT POOR CONTROL OF EYE MOVEMENTS BY THE BRAIN CAN LEAD TO VISION LOSS. HOWEVER, THE NEURAL MECHANISMS THAT CORRECT EYE MOVEMENTS IN RESPONSE TO VISUAL ERRORS (OCULOMOTOR LEARNING) REMAIN INCOMPLETELY UNDERSTOOD. SACCADES, WHICH ARE RAPID EYE MOVEMENTS THAT DIRECT THE FOVEA TO TARGETS, REQUIRE PRECISE ADAPTIVE CONTROL TO ENSURE VISUAL ACCURACY WITHOUT REAL-TIME VISUAL FEEDBACK. ELUCIDATING THIS ADAPTIVE OCULOMOTOR CONTROL IS CRITICAL, AS EYE MOVEMENT DISORDERS WITH CEREBELLAR INVOLVEMENT OFTEN IMPAIR THIS PROCESS AND COMPROMISE ACTIVE VISION. ADAPTIVE CONTROL OF SACCADES DEPENDS ON THE OCULOMOTOR VERMIS (OMV) OF THE CEREBELLUM, WHICH IS ORGANIZED INTO MICROCIRCUITS COMPOSED OF MOLECULAR LAYER INTERNEURONS (MLIS), PURKINJE CELLS (P-CELLS), AND CLIMBING FIBERS. TO DATE, LITTLE IS KNOWN ABOUT THE ROLES OF DISTINCT MLI SUBTYPES AND THEIR INTERACTIONS WITH P-CELLS DURING OCULOMOTOR LEARNING. I HYPOTHESIZE THAT (I) MLIS EXHIBIT PLASTIC CHANGES THAT ARE DISTINCT FROM THOSE OF P-CELLS, AND (II) VISUAL ERROR FEEDBACK FROM CLIMBING FIBERS NOT ONLY INSTRUCTS P-CELLS BUT ALSO MLIS. OVERALL, THE CENTRAL GOALS OF THIS PROPOSAL ARE TO DETERMINE HOW PLASTICITY WITHIN MLIS MODULATES P-CELL OUTPUT TO FACILITATE OCULOMOTOR LEARNING, AND TO DEFINE HOW VISUAL ERROR SIGNALS ARE DISTRIBUTED ACROSS CEREBELLAR MICROCIRCUITS. THIS PROJECT LEVERAGES A LEARNING PARADIGM OF SACCADE ADAPTATION AND HIGH-DENSITY NEURAL RECORDINGS FROM THE OMV IN THE COMMON MARMOSET, A SMALL PRIMATE MODEL UNIQUELY SUITED FOR STUDYING OCULOMOTOR CONTROL AT CELLULAR RESOLUTION. BY UNDERSTANDING HOW CEREBELLAR NEURONS RESPOND TO TYPES OF VISUAL ERRORS AND BEHAVIORAL CONTEXTS, THIS PROJECT WILL DEFINE HOW CEREBELLAR MICROCIRCUITS ADAPT EYE MOVEMENTS. TO INVESTIGATE MY HYPOTHESIS, I PROPOSE THE FOLLOWING AIMS: AIM 1: IDENTIFY THE ROLES OF MLI1S AND MLI2S IN SHAPING P-CELL OUTPUT DURING CEREBELLAR LEARNING. AIM 2: DEFINE THE SPATIOTEMPORAL DYNAMICS OF CLIMBING FIBER INPUT TO P-CELLS AND MLIS DURING VISUAL ERRORS. TOGETHER, THESE STUDIES WILL ENHANCE THE UNDERSTANDING OF HOW ERROR SIGNALS RESHAPE NEURAL CIRCUITS TO SUPPORT PRECISE OCULOMOTOR BEHAVIOR. BY REVEALING FUNDAMENTAL CELL TYPE-SPECIFIC AND CIRCUIT-LEVEL CONTRIBUTIONS TO THE PLASTICITY THAT UNDERLIES ADAPTIVE EYE MOVEMENTS, THIS WORK WILL LAY THE FOUNDATION FOR LEVERAGING ADAPTIVE CEREBELLAR FUNCTION IN TREATMENT APPROACHES FOR PROTECTING AND RESTORING VISION. $0 6/18/26 Not listed THE MEDIATION OF OCULOMOTOR LEARNING BY THE CEREBELLAR CORTEX - PROJECT SUMMARY/ABSTRACT POOR CONTROL OF EYE MOVEMENTS BY THE BRAIN CAN LEAD TO VISION LOSS. HOWEVER, THE NEURAL MECHANISMS THAT CORRECT EYE MOVEMENTS IN RESPONSE TO VISUAL ERRORS (OCULOMOTOR LEARNING) REMAIN INCOMPLETELY UNDERSTOOD. SACCADES, WHICH ARE RAPID EYE MOVEMENTS THAT DIRECT THE FOVEA TO TARGETS, REQUIRE PRECISE ADAPTIVE CONTROL TO ENSURE VISUAL ACCURACY WITHOUT REAL-TIME VISUAL FEEDBACK. ELUCIDATING THIS ADAPTIVE OCULOMOTOR CONTROL IS CRITICAL, AS EYE MOVEMENT DISORDERS WITH CEREBELLAR INVOLVEMENT OFTEN IMPAIR THIS PROCESS AND COMPROMISE ACTIVE VISION. ADAPTIVE CONTROL OF SACCADES DEPENDS ON THE OCULOMOTOR VERMIS (OMV) OF THE CEREBELLUM, WHICH IS ORGANIZED INTO MICROCIRCUITS COMPOSED OF MOLECULAR LAYER INTERNEURONS (MLIS), PURKINJE CELLS (P-CELLS), AND CLIMBING FIBERS. TO DATE, LITTLE IS KNOWN ABOUT THE ROLES OF DISTINCT MLI SUBTYPES AND THEIR INTERACTIONS WITH P-CELLS DURING OCULOMOTOR LEARNING. I HYPOTHESIZE THAT (I) MLIS EXHIBIT PLASTIC CHANGES THAT ARE DISTINCT FROM THOSE OF P-CELLS, AND (II) VISUAL ERROR FEEDBACK FROM CLIMBING FIBERS NOT ONLY INSTRUCTS P-CELLS BUT ALSO MLIS. OVERALL, THE CENTRAL GOALS OF THIS PROPOSAL ARE TO DETERMINE HOW PLASTICITY WITHIN MLIS MODULATES P-CELL OUTPUT TO FACILITATE OCULOMOTOR LEARNING, AND TO DEFINE HOW VISUAL ERROR SIGNALS ARE DISTRIBUTED ACROSS CEREBELLAR MICROCIRCUITS. THIS PROJECT LEVERAGES A LEARNING PARADIGM OF SACCADE ADAPTATION AND HIGH-DENSITY NEURAL RECORDINGS FROM THE OMV IN THE COMMON MARMOSET, A SMALL PRIMATE MODEL UNIQUELY SUITED FOR STUDYING OCULOMOTOR CONTROL AT CELLULAR RESOLUTION. BY UNDERSTANDING HOW CEREBELLAR NEURONS RESPOND TO TYPES OF VISUAL ERRORS AND BEHAVIORAL CONTEXTS, THIS PROJECT WILL DEFINE HOW CEREBELLAR MICROCIRCUITS ADAPT EYE MOVEMENTS. TO INVESTIGATE MY HYPOTHESIS, I PROPOSE THE FOLLOWING AIMS: AIM 1: IDENTIFY THE ROLES OF MLI1S AND MLI2S IN SHAPING P-CELL OUTPUT DURING CEREBELLAR LEARNING. AIM 2: DEFINE THE SPATIOTEMPORAL DYNAMICS OF CLIMBING FIBER INPUT TO P-CELLS AND MLIS DURING VISUAL ERRORS. TOGETHER, THESE STUDIES WILL ENHANCE THE UNDERSTANDING OF HOW ERROR SIGNALS RESHAPE NEURAL CIRCUITS TO SUPPORT PRECISE OCULOMOTOR BEHAVIOR. BY REVEALING FUNDAMENTAL CELL TYPE-SPECIFIC AND CIRCUIT-LEVEL CONTRIBUTIONS TO THE PLASTICITY THAT UNDERLIES ADAPTIVE EYE MOVEMENTS, THIS WORK WILL LAY THE FOUNDATION FOR LEVERAGING ADAPTIVE CEREBELLAR FUNCTION IN TREATMENT APPROACHES FOR PROTECTING AND RESTORING VISION. $55.1k 6/18/26