BDNF Signaling in Glutamatergic Neurons During Long-Term Potentiation (LTP): A Spatio-Temporal Exploration of Events

Long-term potentiation (LTP), a cellular mechanism underlying learning and memory, progresses through three stages-initial, early, and late-each characterized by distinct molecular events that contribute to memory consolidation. What might bind them together is, on the molecular level, the release of brain-derived neurotrophic factor (BDNF) from excitatory neurons. Excitatory neurons release glutamate and, in addition, if stimulated in the right manner, also secrete BDNF. Key signaling pathways mediating BDNF's effects in the process from early to late memory processes include the MAPK/ERK, PI3K/Akt, and PLCγ/IP3 cascades. Notably, glutamate signaling activates PLCβ/IP3, PI3K/Akt, and MAPK/ERK pathways, reinforcing synaptic strength. This review explores the spatio-temporal activation of these pathways across LTP stages, emphasizing the interplay between BDNF and glutamate in shaping the excitatory synaptic plasticity. By mapping these molecular events, we aim to provide a comprehensive framework for understanding how BDNF-driven signaling contributes to neuroplasticity and memory formation.