Figure 2.

Molecular mechanisms of LTP in the hippocampus. The molecular mechanisms underlying LTP, involving signaling pathways mediated by N-methyl-D-aspartate (NMDA) receptors (NMDARs) and calcium ions (Ca²⁺). At excitatory synapses, synaptic plasticity is primarily mediated by alterations in postsynaptic ionotropic glutamate receptors, particularly α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs). NMDARs play a crucial role in initiating LTP by acting as coincidence detectors for pre- and postsynaptic firing patterns. An NMDAR-mediated rise in postsynaptic Ca²⁺ activates the Ca²⁺/Calmodulin (CaM)-dependent protein-kinase II (CaMKII). CaMKII-dependent phosphorylation, in turn, drives AMPAR incorporation to postsynaptic density in a post-synaptic density protein 95 (PSD-95)-dependent manner. Furthermore, CaMKII may phosphorylate cAMP response element-binding protein (CREB), the transcription factor regulating the expression of postsynaptic proteins and driving the physical expansion of dendritic spines. Made with BioRender.