Identifying Connectivity Deficits Between the Cerebellum and the Thalamus in Down Syndrome

Identifying Connectivity Deficits Between the Cerebellum and the Thalamus in Down Syndrome

    Presenter(s)

    Christopher J. Fleisher

    Comments

    Presentation: 10:45-12:00, Kennedy Union Ballroom

    Description

    Down Syndrome (DS) is a genetic disorder marked by behavioral abnormalities impacting diverse brain regions, notably the cerebellum. The cerebellum, a key brain region governing motor coordination, gait, and adaptive learning, exhibits altered developmental trajectories in individuals with DS. This vital region forms an intricate network of connections, known as the 'cerebellar connectome,' during development. Deficits in these connections may lead to dysfunction in not only the cerebellum but other brain regions, such as the thalamus. Our goal- to determine how the connectivity is potentially disrupted between the cerebellum and one of its major targets - the thalamus across postnatal development in a mouse model of DS. To accomplish this, we are using a precise and efficient tracing strategy using viruses to label connections between the cerebellum and the thalamus. Injected viruses in both the source cerebellar nuclei region (Fastigial Nucleus- FN) and the target thalamic nuclei (Ventromedial Nucleus- VM) will enable us to specifically target and visualize the cells in the cerebellar nuclei neuron that project to the Thalamus. These viruses use a genetic recombination system and label only the neurons connecting the two regions with reporter Green Fluorescent Protein. So far, 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). 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 begun injections into the cerebellar and thalamic nuclei.

    Publication Date

    4-17-2024

    Project Designation

    Independent Research

    Primary Advisor

    Aaron S. Sathyanesan

    Primary Advisor's Department

    Biology

    Keywords

    Stander Symposium, College of Arts and Sciences

    Identifying Connectivity Deficits Between the Cerebellum and the Thalamus in Down Syndrome

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