Striatal circuit development and its alterations in Huntington's disease

Abstract

Huntington's disease (HD) is an inherited neurodegenerative disorder that usually starts during midlife with progressive alterations of motor and cognitive functions. The disease is caused by a CAG repeat expansion within the huntingtin gene leading to severe striatal neurodegeneration. Recent studies conducted on pre-HD children highlight early striatal developmental alterations starting as soon as 6 years old, the earliest age assessed. These findings, in line with data from mouse models of HD, raise the questions of when during development do the first disease-related striatal alterations emerge and whether they contribute to the later appearance of the neurodegenerative features of the disease. In this review we will describe the different stages of striatal network development and then discuss recent evidence for its alterations in rodent models of the disease. We argue that a better understanding of the striatum's development should help in assessing aberrant neurodevelopmental processes linked to the HD mutation.

Keywords: Basal ganglia; Huntington's disease; Matrix; Medium spiny neurons; Neuronal excitability; Spiny projection neurons; Striatal development; Striosomes.