Dendritic Inhibition by Shh Signaling-Dependent Stellate Cell Pool Is Critical for Motor Learning

Area of Science:

• Neuroscience
• Developmental Biology
• Cell Biology

Background:

• Cerebellar inhibitory interneurons (MLIs), including basket cells (BCs) and stellate cells (SCs), regulate motor and nonmotor functions.
• MLIs are generated sequentially from Pax2+ progenitors in an inside-out pattern.
• Mechanisms determining MLI subtype identity and pool sizes, and their role in motor learning, remain unclear.

Purpose of the Study:

• Investigate the role of Sonic hedgehog (Shh) signaling in cerebellar inhibitory interneuron development.
• Determine how MLI subtype identity and pool sizes are established.
• Elucidate the contribution of MLI subtypes to motor learning.

Main Methods:

• Utilized conditional Shh signaling manipulation in mice.
• Employed genetic depletion of GABAergic progenitors.
• Assessed proliferation of Pax2+ progenitors and MLI subtype numbers.
• Examined dendritic inhibitory synapses and eyeblink conditioning performance.

Main Results:

• Shh signaling modulates GABAergic progenitor proliferation and Pax2+ cell numbers, selectively impacting SC pool size but not BC numbers.
• MLI subtype specification occurs independently of Shh signaling and birth order, likely after progenitor migration and laminar positioning.
• Reduced SC numbers lead to impaired dendritic inhibition and defective motor learning (eyeblink conditioning).

Conclusions:

• Shh signaling is essential for regulating the number of cerebellar SCs.
• MLI subtype specification is independent of Shh and birth order, occurring post-migration.
• Shh-dependent SCs are critical for inhibitory synaptic function and motor learning.