The presynaptic-based mechanism for learning and memory

Memory formation is based on molecular and cellular processes across synapses, neurons, and neural circuits. While historically focused on postsynaptic mechanisms, cumulating evidence highlights the presynaptic terminal's crucial contributions. Presynaptic plasticity, including neurotransmitter release regulation, vesicle dynamics, active zone remodeling, and energy regulation, enables efficient synaptic transmission and plasticity. Short-term presynaptic plasticity includes facilitation, depression, augmentation, and post-tetanic potentiation, driven by calcium dynamics, vesicle mobilization, and molecular adaptations. Long-term presynaptic plasticity involves enduring changes, such as presynaptic LTP and LTD, essential for learning, synaptic remodeling, and homeostasis. Additionally, activity-dependent structural plasticity dynamically reshapes presynaptic components, enhancing synaptic strength and circuit refinement. Key molecular regulators, including calcium sensors, scaffolding proteins, adhesion molecules, and signaling pathways, mediate these processes. Challenges in isolating presynaptic specific contributions demand advanced techniques, while future research aims to integrate genetic, electrophysiological, and behavioral approaches to unravel presynaptic mechanisms in learning, memory, and cognitive disorders.