Age-Dependent Degradation of Locomotion Encoding in Huntington's Disease R6/2 Model Mice.

Area of Science:

• Neuroscience
• Genetics
• Neurology

Background:

• Huntington's disease (HD) is an inherited neurodegenerative disorder causing brain atrophy.
• The R6/2 transgenic mouse model exhibits motor and cognitive deficits mirroring HD pathology.

Purpose of the Study:

• Investigate how Huntington's disease progression affects striatal movement encoding.
• Analyze neuronal activity changes in the striatum during locomotion in HD models.

Main Methods:

• Chronic neuronal recordings in the dorsal striatum of R6/2 transgenic (Tg) and wild-type (WT) mice.
• Observation of neuronal activity during novel environment exploration to assess locomotion encoding.

Main Results:

• Tg mice showed degraded exploratory locomotion and altered neuron populations (fewer medium spiny neurons, more fast spiking interneurons).
• Medium spiny neurons in Tg mice exhibited altered bursting, while fast spiking interneurons showed reduced firing rates and increased task-responsiveness.
• Striatal neurons in Tg mice demonstrated reduced locomotion encoding, with fast spiking interneurons significantly affected in older mice.

Conclusions:

• Striatal information processing declines with age in Huntington's disease transgenic mice.
• The capacity of fast spiking interneurons to compensate for medium spiny neuron loss diminishes as the disease progresses.
• This neuronal dysfunction likely contributes to the observed age-dependent decline in exploratory locomotion in HD models.