Presynaptic homeostasis mediated by exocytosis of a SNARE protein.

High-frequency stimulation triggers presynaptic homeostasis that reduces neurotransmitter release independently of postsynaptic receptors via v-SNARE VAMP7.

• Why it matters: Neural circuits need homeostatic mechanisms to keep stable responsiveness, but how activity changes are converted into altered neurotransmission has been unclear.
• What they did: The study shows VAMP7 reduces release by inhibiting Ca2+ entry through P/Q-type presynaptic Ca2+ channels, requiring the t-SNARE syntaxin and AP-3–derived vesicle delivery.
• The result: This metaplasticity operates across multiple excitatory synapses, and without it the fraction of FOS+ neurons increases several fold, linking VAMP7-dependent regulation to activity-dependent sparsity.