Figure 1.

Hypothetical mechanism of PGE₂-mediated LTP in the visual cortex. TBS produces arachidonic acid (AA) from the membrane lipid substrate. AA is metabolized to PGH₂ by COX-2 that has been activated concomitantly by TBS. PGH₂ is converted immediately to PGE₂ by PGE₂ synthase. EP2 translocates from the cytosol to the membrane, simultaneously, with the translocation of EP3 from the membrane to the cytosol. The PGE₂ that is generated spreads from postsynaptic sites into the synaptic cleft, where it activates EP2 at the postsynaptic membrane, resulting in the production of cAMP. Subsequently, cAMP activates PKA, which in turn activates CREB in the nucleus of postsynaptic cells in the visual cortex. This activation of CREB may induce the synthesis of proteins such as BDNF, which is involved in the L-LTP.