Striosomes Mediate Value-Based Learning Vulnerable in Age and a Huntington's Disease Model

Area of Science:

• Neuroscience
• Behavioral Science
• Computational Neuroscience

Background:

• Valence-based learning, essential for survival, involves judging the relative value of options.
• The striatum, a key brain structure, plays a role in reward-based learning and decision-making.

Purpose of the Study:

• To investigate the role of striosomal and matrix compartments of the striatum in valence-based learning.
• To explore the neural mechanisms underlying discrimination learning and task engagement.

Main Methods:

• Utilizing engineered mice and calcium imaging to monitor neural activity during learning tasks.
• Employing chemogenetics to manipulate neuronal activity and computational modeling to analyze circuit function.

Main Results:

• Striosomal, but not matrix, striatal activity selectively correlated with valence-based learning and task engagement.
• Striosomal function was impaired with aging and in a Huntington's disease mouse model.
• Enhanced connectivity of fast-spiking interneurons (FSIs) to projection neurons within striosomes was observed in learning mice.

Conclusions:

• The striosome compartment is critical for learning to differentiate between favorable and unfavorable options.
• FSIs within striosomes may modulate signal-to-noise ratio, facilitating discrimination and learning.
• Dysfunction in striosomal circuits contributes to learning deficits in aging and Huntington's disease.