Figure 3.

Molecular mechanisms of learning. When an animal encodes a new memory (such as the encounter of food in a particular arm of a Y-maze, upper panel), a subset of neurons gets activated and an engram is formed (purple neurons, middle panel). Certain synapses in between engram cells (dotted lines) undergo synaptic plasticity changes (early long-term potentiation [LTP]). The (1) neurotransmitter glutamate (Glu) is released from the presynaptic neuron, Glu binds to (2) AMPARs in the postsynaptic membrane, at the level of the dendritic spine, allowing K⁺ and Na⁺ to enter the postsynaptic neuron and depolarizing it (3). The positive charges inside the postsynaptic neurons allow the release of the Mg²⁺ ion from the NMDARs and if the Glu release is sustained enough, it will open the channel (4). Ca²⁺ enters the postsynaptic neuron, activating the (5) Ca²⁺/calmodulin-dependent protein kinase II (CaMKII). CaMKII phosphorylates AMPARs (6) to increase their sensitivity to Glu and drives more active channels to the membrane, AMPA trafficking (7). The number and shape of dendritic spines also get modified during learning. Spine remodeling to strengthen the synapse involves cytoskeletal modification such as (A) actin polymerization and (B) actin branching. Engram cells become unsilenced by the trafficking of AMPAR to the synapses by (C) secretion from the intracellular pool and (D) diffusion from other membrane areas. AMPAR, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor; NMDAR, N-methyl-d-aspartate receptor.