The mediation of oculomotor learning by the cerebellar cortex

The National Eye Institute, part of the Department of Health and Human Services National Institutes of Health, awarded The Johns Hopkins University $110,228 on February 12, 2027, under the Vision Research program (CFDA 93.867) to conduct research on the mediation of oculomotor learning by the cerebellar cortex.

The funded research investigates how molecular layer interneurons and Purkinje cells within the cerebellar cortex's oculomotor vermis adapt rapid eye movements (saccades) in response to visual errors. The project uses high-density neural recordings and saccade adaptation paradigms in common marmosets to determine how plasticity within molecular layer interneurons modulates Purkinje cell output and how visual error signals distribute across cerebellar microcircuits. The research addresses the neural mechanisms underlying adaptive oculomotor control, with implications for understanding and treating eye movement disorders that impair active vision.

Performance will occur in Baltimore, Maryland, with a period of performance extending from the award date through June 30, 2029. The award is classified as a Project Grant, an assistance type used by the National Eye Institute to support innovative research that advances vision science and clinical applications.

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.