| Entry |
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| Name |
Long-term potentiation
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| Description |
Hippocampal long-term potentiation (LTP), a long-lasting increase in synaptic efficacy, is the molecular basis for learning and memory. Tetanic stimulation of afferents in the CA1 region of the hippocampus induces glutamate release and activation of glutamate receptors in dendritic spines. A large increase in [Ca2+]i resulting from influx through NMDA receptors leads to constitutive activation of CaM kinase II (CaM KII) . Constitutively active CaM kinase II phosphorylates AMPA receptors, resulting in potentiation of the ionic conductance of AMPA receptors. Early-phase LTP (E-LTP) expression is due, in part, to this phosphorylation of the AMPA receptor. It is hypothesized that postsynaptic Ca2+ increases generated through NMDA receptors activate several signal transduction pathways including the Erk/MAP kinase and cAMP regulatory pathways. The convergence of these pathways at the level of the CREB/CRE transcriptional pathway may increase expression of a family of genes required for late-phase LTP (L-LTP).
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| Class |
Organismal Systems; Nervous system
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| Pathway map |
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| Other DBs |
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| Orthology |
| glutamate receptor 1 | | glutamate receptor 2 | | | | | | | | protein phosphatase 1, regulatory (inhibitor) subunit 1A | | protein phosphatase 1, catalytic subunit [EC: 3.1.3.16] | | protein phosphatase 1 regulatory subunit 12A | | protein phosphatase 1 regulatory subunit 12B | | calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC: 2.7.11.17] | | Rap guanine nucleotide exchange factor (GEF) 3 | | Ras-related protein Rap-1A | | Ras-related protein Rap-1B | | protein phosphatase 3, catalytic subunit [EC: 3.1.3.16] | | protein phosphatase 3, regulatory subunit | | glutamate receptor ionotropic, NMDA 1 | | glutamate receptor ionotropic, NMDA 2A | | glutamate receptor ionotropic, NMDA 2B | | glutamate receptor ionotropic, NMDA 2C | | glutamate receptor ionotropic, NMDA 2D | | voltage-dependent calcium channel L type alpha-1C | | calmodulin | | | | cyclic AMP-dependent transcription factor ATF-4 | | calcium/calmodulin-dependent protein kinase IV [EC: 2.7.11.17] | | GTPase HRas | | GTPase KRas | | GTPase NRas | | A-Raf proto-oncogene serine/threonine-protein kinase [EC: 2.7.11.1] | | B-Raf proto-oncogene serine/threonine-protein kinase [EC: 2.7.11.1] | | RAF proto-oncogene serine/threonine-protein kinase [EC: 2.7.11.1] | | mitogen-activated protein kinase kinase 1 [EC: 2.7.12.2] | | mitogen-activated protein kinase kinase 2 [EC: 2.7.12.2] | | extracellular signal-regulated kinase 1/2 [EC: 2.7.11.24] | | | | inositol 1,4,5-triphosphate receptor type 1 | | inositol 1,4,5-triphosphate receptor type 2 | | inositol 1,4,5-triphosphate receptor type 3 | | | | metabotropic glutamate receptor 1 | | metabotropic glutamate receptor 5 | | guanine nucleotide-binding protein G(q) subunit alpha | | phosphatidylinositol phospholipase C, beta [EC: 3.1.4.11] |
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| Compound |
| L-Glutamate | | Calcium cation | | Diacylglycerol | | Magnesium cation | | 3',5'-Cyclic AMP | | D-myo-Inositol 1,4,5-trisphosphate | | Sodium cation |
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| Reference |
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| Authors |
Blitzer RD, Iyengar R, Landau EM. |
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| Title |
Postsynaptic signaling networks: cellular cogwheels underlying long-term plasticity. |
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| Journal |
Biol Psychiatry 57:113-9 (2005) |
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| Reference |
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| Authors |
Soderling TR, Derkach VA. |
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| Title |
Postsynaptic protein phosphorylation and LTP. |
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| Journal |
Trends Neurosci 23:75-80 (2000) |
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| Reference |
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| Authors |
Poser S, Storm DR. |
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| Title |
Role of Ca2+-stimulated adenylyl cyclases in LTP and memory formation. |
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| Journal |
Int J Dev Neurosci 19:387-94 (2001) |
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| Reference |
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| Authors |
Xia Z, Storm DR. |
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| Title |
The role of calmodulin as a signal integrator for synaptic plasticity. |
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| Journal |
Nat Rev Neurosci 6:267-76 (2005) |
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| Reference |
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| Authors |
Purves D, Augustine GJ (ed). |
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| Title |
Neuroscience |
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| Journal |
Sunderland, Mass.:Sinauer Associates (2004) |
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| Reference |
(Japanese) |
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| Authors |
Futai K, Hayashi Y. |
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| Title |
[Molecular mechanisms of hippocampal long-term potentiation.] (In Japanese) |
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| Journal |
Experimental Medicine 21(17):2361-2369 (2003) |
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| Reference |
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| Authors |
Lynch MA. |
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| Title |
Long-term potentiation and memory. |
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| Journal |
Physiol Rev 84:87-136 (2004) |
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| Reference |
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| Authors |
Kelly PT, Mackinnon RL 2nd, Dietz RV, Maher BJ, Wang J. |
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| Title |
Postsynaptic IP3 receptor-mediated Ca2+ release modulates synaptic transmission in hippocampal neurons. |
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| Journal |
Brain Res Mol Brain Res 135:232-48 (2005) |
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| Reference |
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| Authors |
Berridge MJ. |
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| Title |
Neuronal calcium signaling. |
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| Journal |
Neuron 21:13-26 (1998) |
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