Characteristics of excitatory synapses and mutant huntingtin distribution in the Q175 mouse model of Huntington’s disease

• Main Author: Chen, Dickson Tik Sang
• Other Authors: Luebke, Jennifer I.
• Language: en_US
• Published: 2021
• Subjects: Neurosciences; Axospinous; Basal ganglia; Rostral-caudal axis; Striatum; Thalamostriatal; Thalamus
• Online Access: https://hdl.handle.net/2144/43338

Huntington’s disease is an inherited neurodegenerative disease characterized by the degeneration of the cerebral cortex, thalamus, and striatum. The loss of neurons in the cerebral cortex and the thalamus may affect the synaptic circuitry in the striatum as these regions send glutamatergic projections (corticospinal & thalamostriatal) to neurons in the striatum. Prior studies have suggested the detrimental impact that the mutant Huntingtin protein (mHTT) may have on corticostriatal afferents, but less is known thalamic inputs to the dorsal striatum. In this study, we report a 50% reduction in thalamostriatal axospinous synapse density and significant reductions in dendritic spine volume at the ultrastructural level using electron microscopy. Additionally, dystrophic alterations to mitochondria size and morphology were also found. At the microcircuit level, we report a reduction in the spatial abundance of thalamostriatal axon terminals at the rostral, middle, and caudal levels of the dorsolateral striatum while an inverse distribution was observed for mHTT, suggesting a novel topographic distribution of thalamostriatal projections and mHTT along the rostral-caudal axis of the dorsolateral striatum. These findings are novel in the Q175 HD mouse model and supports the theory of an excitatory: inhibitory imbalance contributing to structural synaptic changes in the dorsal striatum. Further studies of the corticostriatal projections will determine the global extent of this imbalance.