Synaptic pathology in Huntington's disease: Beyond the corticostriatal pathway

Area of Science:

• Neuroscience
• Genetics
• Neurodegenerative Diseases

Background:

• Huntington's disease (HD) is an inherited neurodegenerative disorder caused by a mutation in the Huntingtin gene.
• HD pathology includes significant neuronal loss in the striatum and other brain regions within the cortico-basal ganglia-thalamocortical (CBGTC) loop.
• The mutant huntingtin protein plays a crucial role in synaptic transmission, a function increasingly recognized as vital in HD pathogenesis.

Purpose of the Study:

• To review morphological and electrophysiological alterations in pathways affected by Huntington's disease.
• To investigate the impact of the Huntingtin gene mutation on synaptic function beyond the striatum and cerebral cortex.
• To synthesize current knowledge on how Huntington's disease affects neuronal pathways in animal models.

Main Methods:

• Review of existing literature on Huntington's disease animal models.
• Analysis of studies focusing on morphological changes in affected neural pathways.
• Examination of electrophysiological data related to synaptic transmission in HD models.

Main Results:

• Accumulating evidence indicates pervasive synaptic disconnection in Huntington's disease models.
• Excitatory pathways appear particularly affected by synaptic disconnection.
• These findings underscore the critical role of the huntingtin protein in maintaining normal synaptic transmission.

Conclusions:

• Synaptic disconnection is a near-universal feature in Huntington's disease, impacting multiple neural pathways.
• The huntingtin protein is essential for proper synaptic function.
• Further research into these altered pathways is crucial for understanding and treating Huntington's disease.