mTOR signaling contributes to motor skill learning in mice

Area of Science:

• Neuroscience
• Molecular Biology
• Motor Control Research

Background:

• The mammalian target of rapamycin (mTOR) kinase regulates mRNA translation and is implicated in synaptic and behavioral plasticity.
• The specific role of mTOR in motor learning and control has not been previously investigated.

Purpose of the Study:

• To investigate the involvement of mTOR in the motor learning processes using the accelerating rotarod task in mice.
• To determine if mTOR inhibition affects motor abilities versus motor learning.

Main Methods:

• Assessed mTOR levels (total and phosphorylated) in brain regions of mice trained on an accelerating rotarod.
• Utilized systemic and intrastriatal rapamycin (mTOR inhibitor) and intrastriatal mTOR siRNA (genetic knockdown) to inhibit mTOR.
• Evaluated motor learning via rotarod performance and motor abilities using the pole test.
• Measured downstream targets of mTORC1, including phosphorylated 4EBP1 and P70S6K.

Main Results:

• Rotarod learning increased phosphorylated mTOR in the striatum and hippocampus during the initial training session.
• Systemic and striatal inhibition of mTOR significantly reduced rotarod performance, indicating impaired motor skill consolidation.
• Motor abilities, assessed by the pole test, remained unaffected by mTOR inhibition.
• All mTOR inhibition treatments decreased the phosphorylation of 4EBP1 and P70S6K.

Conclusions:

• Striatal mTOR kinase plays a significant role in the cellular and molecular mechanisms underlying motor skill learning.
• mTOR activity, specifically via phosphorylation of 4EBP1 and P70S6K, is critical for motor learning consolidation, not general motor execution.