Presenter(s)

Samantha Bailey, Mir Abbas Raza, Ashlynn Prater, Alaina Sharp

Comments

9:00-10:15, Kennedy Union Ballroom

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Description

Down syndrome (DS) is a neurodevelopmental disorder caused by the triplication of human chromosome 21. The cerebellum plays a critical role in motor coordination and adaptive motor learning. Individuals with DS exhibit deficits in functional and adaptive motor behavior across development. A deficit in cerebellar volume, or hypoplasia is a hallmark of DS, and is mirrored in preclinical mouse models. What remains unknown is the underlying circuit dysfunction contributing to these behaviour abnormalities. Our objective is to investigate the connectivity deficits in the cerebellum throughout postnatal development and its role in behavioral abnormalities in the Ts65Dn mouse model of DS. In this study, we have used the ErasmusLadder to assess deficits in Locomotor coordination and cerebellar-dependent adaptive behavior in Euploid and Trisomic mice. Synaptic density of Parallel fiber and Climbing fiber input was quantified using Immunohistochemistry (IHC) and analyzed with python. Our results show that the Ts65Dn mice models displayed distinct deficits in both locomotor coordination and adaptive behavior across juvenile (P30) and young-adult (P45) stages. We found no significant differences for absolute learning exhibited in the euploid (wild type) in comparison to trisomic mice at P30. However, there was a significant decline of absolute learning behavior for the Ts65Dn at P45. Machine-learning enabled quantification showed significant reduction in VGLUT2 synaptic density via climbing fiber input onto Purkinje cells (PCs), but no significant difference in VGLUT1 synaptic density via parallel fiber input at P45. Findings indicate abnormalities in cerebellar-dependent adaptive learning at P45 could be a result of circuit deficits in climbing fiber synaptic input onto PCs. We are currently analysing potential synaptic density changes at P30 as well. Further investigation of these circuit deficits using Fiber Photometry would contribute to a deeper understanding of DS-related motor impairments and lead to potential therapeutic interventions.

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; Vocation

Identifying Mechanisms of Cerebellar Circuit Dysfunction in the Ts65Dn Model of Down Syndrome

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