Exploring Neural Circuitry and Purkinje Cell Changes Underlying Cerebellum-Dependent Motor Abnormalities in Down Syndrome

Date of Award

5-5-2024

Degree Name

M.S. in Biology

Department

Department Biology

Advisor/Chair

Aaron Sathyanesan

Abstract

Down syndrome (DS) is a commonly diagnosed neurodevelopmental disorder and is caused by the triplication of human chromosome 21 (Trisomy 21). Individuals with DS have a broad range of behavioral deficits in cognitive and motor domains. From previous studies, it has been found that the cerebellum - a region of the brain that is critical for locomotor learning and coordination - has altered developmental trajectory in DS. This includes atypical development of purkinje cells (PCs) which are the sole output neurons for the cerebellar cortex that impacts locomotor behavior. Previous studies have shown that these inputs are important for proper motor learning. However, it is unknown if the motor deficits in DS are caused by altered synaptic input in the PCs. The aims of my research include defining potential changes in PC synaptic input in the Ts65Dn mouse model of DS by using immunohistochemistry (IHC) and determining gait and cerebellum-dependent learning abnormalities using the Erasmus Ladder. Future experiments will be targeted towards continuing to make connections between the circuitry and behavioral tests to advance the understanding of how altered brain circuitry in DS causes atypical behavioral outcomes in children.

Keywords

Neurodevelopmental Disorder, Down syndrome, Trisomy 21, Cerebellum, Motor Deficits, Behavior Deficits, Investigating Circuitry and Behavior, Immunohistochemistry, ErasmusLadder

Rights Statement

Copyright 2024, author

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