Long‐term Depression and Depotentiation


Long‐term depression and depotentiation are activity‐dependent processes that weaken synapses. These processes are thought to work together with long‐term potentiation to encode memory.

Keywords: long‐term potentiation; depotentiation; learning; metabotropic glutamate receptor; glutamate receptor

Figure 1.

The dominant mechanism for expressing long‐term depression is a decrease in AMPA receptor‐mediated currents (GluR1‐3). The removal of AMPA receptors from the synapse is triggered by a specific phosphorylation of the GluR1 receptor and a specific dephosphorylation of the GluR2 receptor as described in the figure. The activities of the respective kinase and phosphatase are controlled indirectly by a limited increase in spine Ca2+ levels. Ca2+ enters the spine either through NMDA receptors activated by glutamate or by release from intracellular stores. The signal for release from intracellular stores derives from glutamate activation of the metabotropic glutamate receptor (mGluR), sequential effects of g protein (Gq/11), phospholipase C (PLC), and inositol 1,4,5‐trisphosphate (IP3). Ca2+ also activates nitric oxide synthase (NOS). Nitric oxide (NO) can mediate a decrease in the release of glutamate. Other abbreviations: PKC, protein kinase C; GRIP, glutamate receptor interacting protein; PICK, protein interacting with C‐kinase; AP2, assembly/adaptor proteins‐2; Ras‐GRF1, ras guanine nucleotide releasing factor 1; p38MAPK, p38 mitogen‐activated protein kinase; PP2b, protein phosphatase 2B; LIMK, lin‐11 isl‐1 mec‐3 motif kinase; PKA, protein kinase A; AKAP, A‐kinase anchoring protein; PP1, protein phosphatase 1.



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Further Reading

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Wagner JJ and Alger BE (1996) Homosynaptic LTD and depotentiation: do they differ in name only? Hippocampus 6(1): 24–29.

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Lisman, John, and Richard, Edwin A(Sep 2007) Long‐term Depression and Depotentiation. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000164.pub2]