Presenter(s)

Samantha Bailey, Alaina Sharp

Comments

9:00-10:15, Kennedy Union Ballroom

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Description

Down Syndrome (DS) is a neurodevelopmental disorder characterized by behavioral abnormalities in multiple brain regions. The cerebellum, a key regulator of motor coordination and learning, shows hypoplasia and reduced connectivity in individuals with DS with preclinical models mirroring this phenotype. Clinical imaging studies have shown volumetric reduction in cerebellar afferent tracts suggesting impaired communication with other brain regions. The cerebellum also forms extensive output connections with the thalamus, a critical relay center for motor and sensory processing, over a prolonged developmental timeline. However, the extent to which cerebellar-thalamic connectivity is potentially altered across postnatal development in mice models of DS remains unknown. Potential changes in cellular density of cerebellar nuclei were assessed using immunohistochemistry (IHC), and the alteration in neural circuitry was quantified using dual Adeno-Associated Viral (AAV) injections combined with IHC and image processing using the QUINT workflow. At postnatal day 30 (P30), no significant differences were observed in cellular density of osteopontin positive cells in the cerebellar nuclei between Euploid and Trisomic Ts65Dn mice and quantification for P45 is underway. An anterograde AAV expressing GFP was injected into the interposed cerebellar nuclei, while a retrograde AAV expressing Cre-recombinase was injected into the lateral-ventral thalamus and successfully labeled connections between these areas. Co-localization of fluorescent markers allowed for visualization of cerebellar-thalamic connectivity at P45 (n=4 each Euploid and Trisomic). Analysis of these injections is underway with experiments planned to extend assessment to later developmental stages to determine whether connectivity disruptions emerge over time. Understanding these developmental circuit alterations will help elucidate the mechanisms underlying behavioral deficits in DS and may provide avenues for targeted interventions to address motor and cognitive deficits in affected individuals.

Publication Date

4-23-2025

Project Designation

Independent Research

Primary Advisor

Aaron S. Sathyanesan

Primary Advisor's Department

Biology

Keywords

Stander Symposium, College of Arts and Sciences

Institutional Learning Goals

Scholarship

Identifying Connectivity Deficits Between the Cerebellum and Thalamus in Down Syndrome

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