Determining potential connectivity deficits between the Cerebellum and the thalamus in Ts65Dn mouse model of Down syndrome

Determining potential connectivity deficits between the Cerebellum and the thalamus in Ts65Dn mouse model of Down syndrome

Presenter(s)

Mir Abbas Raza

Comments

11:00-12:30, Kennedy Union 222

Description

Down Syndrome is a neurodevelopmental disorder caused by triplication in human chromosome 21 and characterised by alteration in cognitive and motor behaviour. The cerebellum - a key brain region that regulates gait, motor coordination, and adaptive learning - has an altered developmental trajectory in Down Syndrome, with preclinical mouse models mirroring these phenotypes. During development, the cerebellum not only forms its internal circuitry but also forms an extensive connectome with other major regions of the brain including the thalamus. However, potential connectivity deficits between the cerebellum and its connections with other regions of the brain in DS remain unknown. In this study, 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 analysis 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 the same in developmental stage 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 as well as assessment of functional connectivity using Fiber photometry. 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

Graduate Research

Primary Advisor

Aaron S. Sathyanesan

Primary Advisor's Department

Biology

Keywords

Stander Symposium, College of Arts and Sciences

Institutional Learning Goals

Scholarship; Vocation

Determining potential connectivity deficits between the Cerebellum and the thalamus in Ts65Dn mouse model of Down syndrome

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