Synaptic Dysfunction in Huntington's Disease: Lessons from Genetic Animal Models

The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry
Carlos Cepeda, Michael S Levine

Abstract

The understanding of the functional and structural changes occurring in the cerebral cortex and basal ganglia in Huntington's disease (HD) has benefited considerably from the generation of genetic animal models. Most studies of synaptic alterations in HD models have focused on the striatum, but a more complete picture of synaptic dysfunction in the cortico-basal ganglia-cortical loop is emerging. Here, we provide a review and analysis of current developments in the study of synaptic alterations in these areas using HD rodent models. Recent evidence indicates that cortical maldevelopment plays a role in synaptic dysfunction along the corticostriatal pathway that may have its roots in the way mutant huntingtin interacts with synaptic proteins. Furthermore, a progressive disconnection in the corticostriatal pathway leads to abnormal function engaging extrasynaptic N-methyl-D-aspartate glutamate receptors that contribute to eventual cell degeneration. In addition, biphasic increases followed by decreases in glutamate and dopamine release in the striatum could explain contrasting symptomatology in early and late stages of the disease. Changes in striatal output regions also are beginning to be examined. Finally, we highlight some th...Continue Reading

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Citations

Jun 11, 2021·Frontiers in Neuroanatomy·Vyshnavi RallapalleMichelle Gray
Aug 17, 2021·Pediatric Neurology·Nina F Schor, Diana W Bianchi

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