Determining connectivity deficits between the cerebellum and the thalamus in the Ts65Dn mouse model of Down Syndrome.

Determining connectivity deficits between the cerebellum and the thalamus in the Ts65Dn mouse model of Down Syndrome.

Presenter(s)

FNU Mir Abbas Raza

Comments

Presentation: 2:40-3:00, LTC Team Space

Description

Introduction: 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 within the cerebellum and its connections with other regions of the brain in DS remain unknown.

Methods: In this study, we stereotactically injected promoter-specific Cre-expressing retrograde Adeno Associated Viruses (AAVs) and Cre-dependent anterograde AAVs tagged with GFP to specifically label neural projections from the Cerebellar cortex to the Ventromedial thalamic nucleus (VM) via the Fastigial Cerebellar Nucleus (FN) in both Euploid and Trisomic Ts65Dn mice at postnatal day 45. Using confocal images of brain sections after signal enhancement with Immunohistochemistry we analyzed the morphology of the labeled cells, including their dendritic and axonal arborizations, as well as their connectivity patterns using Fiji. We performed descriptive statistical analysis to validate the AAV expression using MATLAB.

Results: We have successfully labeled Purkinje cells through injections into the cerebellar cortex. Our injections into the simplex lobule of the cerebellar cortex of the Euploid Ts65Dn mice have yielded an 82.5% co-localization of 5.4 ± 0.3 Purkinje cells/(100µm)2 labeled with the Cre-dependent GFP expressing AAV out of the 6.6 ± 0.6 Purkinje cells/(100µm)2 immuno-positive for Calbindin (n=2).

Conclusion: Our initial injections show good labeling and high colocalization of the Purkinje cells labeled with GFP in the cerebellar cortex. We are currently working on more injections into the cerebellar cortex and have also begun injections into the cerebellar and thalamic nuclei.

Publication Date

4-17-2024

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; Scholarship; Scholarship

Determining connectivity deficits between the cerebellum and the thalamus in the Ts65Dn mouse model of Down Syndrome.

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