How can long-term sensitization change the number of active zones at nerve terminals?

In the context of neuroplasticity, long-term sensitization leads to an increase in the number of active zones at nerve terminals.1

While short-term sensitization is primarily driven by presynaptic facilitation involving the second messenger cAMP, long-term changes involve structural modifications to the synapse. These active zones—specialized thickened areas of the presynaptic membrane where synaptic vesicles cluster—are essential for the release of neurotransmitters. By increasing the number of these zones, the neuron enhances its synaptic efficacy, allowing for more robust communication between cells. This structural growth serves as a mechanism for long-term memory and demonstrates the adaptive capacity of the nervous system.12