Synaptic vesicle undocking induces low-frequency depression.

Low-frequency depression (LFD) at mammalian synapses results from synaptic vesicle undocking, not depletion of the readily releasable pool, and is immediately reversible by high-frequency stimulation.

• Why it matters: Understanding the mechanisms of synaptic depression is crucial for insights into synaptic transmission and plasticity, especially since LFD occurs at low frequencies where depletion models predict minimal depression. This knowledge can impact how we interpret synaptic behavior in neural circuits.
• What they did: The study counted synaptic vesicles at individual active zones during LFD, revealing that LFD does not depend on vesicle consumption, and proposed a model where undocking causes depression, with recovery depending on stimulation frequency and vesicle docking dynamics.
• The result: Findings suggest that LFD is caused by vesicle undocking rather than depletion, with recovery facilitated by high-frequency stimulation, enabling a better understanding of how stimulation frequency influences short-term synaptic plasticity.