Myosin II regulates activity dependent compensatory endocytosis at central synapses

Area of Science:

• Neuroscience
• Cell Biology
• Synaptic Plasticity

Background:

• Endocytosis, not exocytosis, may limit neurotransmitter release during sustained activity, determining synaptic fatigue.
• Compensatory endocytosis couples retrieval rates to release rates, but the mechanism remains unclear.

Purpose of the Study:

• Investigate the role of presynaptic myosin II (MII) in synaptic vesicle retrieval and neurotransmitter release.
• Differentiate presynaptic from postsynaptic functions of MII using a novel neural circuit technique.

Main Methods:

• Developed live cell substrate patterning for defined, small neural circuits.
• Inactivated MII using blebbistatin and utilized MIIB knock-out cells.
• Assessed synaptic release and retrieval using FM1-43 and horseradish peroxidase.

Main Results:

• MII inactivation significantly inhibited evoked release but not spontaneous release.
• Loss of presynaptic MIIB function decreased evoked release amplitude.
• MII inactivation slowed vesicular replenishment of the recycling pool without affecting release.

Conclusions:

• Presynaptic MII regulates synaptic vesicle retrieval via tension or actin dynamics.
• Changes in retrieval rates dictate recycling pool size and consequently synaptic strength.
• MII plays a key role in maintaining synaptic function during sustained activity.