Friday, March 14, 2025
3/14/2025
ABSTRACT Efficient sensory processing requires the development of precisely wired circuits. Sensory deficits are common in neurodevelopmental disorders (NDDs), such as fragile X syndrome (FXS), underscoring the importance of proper wiring. Despite this, the mechanisms underlying precise sensory circuit wiring and the etiology of sensory dysfunction in NDDs remain poorly understood, precluding development of effective therapies. To address these gaps in knowledge, we have utilized the visual circuitry of the mouse superior colliculus (SC) to elucidate fundamental mechanisms of circuit wiring and uncovered novel sub-circuit-specific visual deficits in FXS mice (Fmr1-/y). In the parent proposal to this supplement, we focus on the mechanisms by which topographic maps of space encoded by retinal ganglion cells (RGCs) in the eye and Layer 5 neurons in primary visual cortex (L5V1) are brought into alignment in the SC. Previous studies by us and others suggest that each stage of visual circuit development in the SC - RGC mapping, visual map alignment, and circuit consolidation - is dependent on neuronal activity; however, the mechanisms underlying each are poorly understood. Based on our previous and preliminary data, we propose a model in which the activity-dependent mechanisms underlying each stage of visual circuit development in the SC are distinct. We will test this model in three specific aims, leveraging a unique combination of cutting-edge techniques and novel genetic mouse models. In this supplement, we will focus on Aim 2 of the parent grant in which we will explore the region- and stage-specific roles of Fmr1, leveraging anatomical tracing and in vivo electrophysiological methods. In addition, we will expand the scope of this aim to determine the region- and stage-specific roles of Fmr1 in establishment of circuits regulating an innate behavior regulated by the SC, namely prey capture. These studies will not only advance our understanding of circuit assembly in the visual system and provide novel insights to sensory dysfunction in FXS, but also provide a rich training opportunity for the candidate. Indeed, the candidate will learn several novel techniques to add to his experimental toolbox, develop skills in data analysis, data presentation, and scientific communication, and build professional skills and networks to help him launch a successful career in health-related research.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).