Learning new sequential stepping patterns requires striatal plasticity during the earliest phase of acquisition

Area of Science:

• Neurobiology
• Motor Control
• Learning and Memory

Background:

• Motor behavior requires adaptable strategies based on environmental cues.
• The neurobiological underpinnings of adapting complex motor skills are not fully understood.

Purpose of the Study:

• To investigate the neural mechanisms of adapting motor behavior to changing environmental conditions.
• To identify brain regions and neuronal pathways involved in learning new locomotor strategies.

Main Methods:

• Mice ran on a motor-driven wheel with changing foothold peg patterns for water reward.
• Measured performance accuracy and water reward achievement.
• Assayed c-Fos expression, in situ hybridization, and immunohistochemistry in striatal sections.
• Blocked N-methyl-D-aspartate (NMDA) receptors in the dorsolateral striatum using AP5.

Main Results:

• Performance and reward acquisition improved after peg pattern changes, indicating successful learning.
• High c-Fos expression was observed in the dorsolateral striatum and motor cortex post-switch.
• Both direct (Substance P+) and indirect (enkephalin+) pathway neurons, along with nNOS interneurons, were recruited in the striatum.
• NMDA receptor blockade in the dorsolateral striatum delayed early performance improvements.

Conclusions:

• The dorsolateral striatum is activated upon environmental shifts to adapt motor behavior via NMDA-dependent plasticity.
• This plasticity is crucial for forming and breaking habits and may relate to clinical disorders.
• The study highlights the role of the striatum in flexible motor skill acquisition.