KEGG   PATHWAY: ko04720Help
Entry
ko04720                     Pathway                                

Name
Long-term potentiation
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).
Class
Organismal Systems; Nervous system
BRITE hierarchy
Pathway map
ko04720  Long-term potentiation
ko04720

Ortholog table
Other DBs
BSID: 496
GO: 0048169
Orthology
K05197  glutamate receptor 1
K05198  glutamate receptor 2
K08041  adenylate cyclase 1 [EC:4.6.1.1]
K08048  adenylate cyclase 8 [EC:4.6.1.1]
K04345  protein kinase A [EC:2.7.11.11]
K08050  protein phosphatase 1 regulatory subunit 1A
K06269  serine/threonine-protein phosphatase PP1 catalytic subunit [EC:3.1.3.16]
K04515  calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17]
K08014  Rap guanine nucleotide exchange factor 3
K04353  Ras-related protein Rap-1A
K07836  Ras-related protein Rap-1B
K04348  serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16]
K06268  serine/threonine-protein phosphatase 2B regulatory subunit
K05208  glutamate receptor ionotropic, NMDA 1
K05209  glutamate receptor ionotropic, NMDA 2A
K05210  glutamate receptor ionotropic, NMDA 2B
K05211  glutamate receptor ionotropic, NMDA 2C
K05212  glutamate receptor ionotropic, NMDA 2D
K04850  voltage-dependent calcium channel L type alpha-1C
K02183  calmodulin
K04498  E1A/CREB-binding protein [EC:2.3.1.48]
K04374  cyclic AMP-dependent transcription factor ATF-4
K05869  calcium/calmodulin-dependent protein kinase IV [EC:2.7.11.17]
K02833  GTPase HRas
K07827  GTPase KRas
K07828  GTPase NRas
K08845  A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04365  B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04366  RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369  mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04371  mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04373  ribosomal protein S6 kinase alpha-1/2/3/6 [EC:2.7.11.1]
K04958  inositol 1,4,5-triphosphate receptor type 1
K04959  inositol 1,4,5-triphosphate receptor type 2
K04960  inositol 1,4,5-triphosphate receptor type 3
K02677  classical protein kinase C alpha type [EC:2.7.11.13]
K19662  classical protein kinase C beta type [EC:2.7.11.13]
K19663  classical protein kinase C gamma type [EC:2.7.11.13]
K04603  metabotropic glutamate receptor 1
K04604  metabotropic glutamate receptor 5
K04634  guanine nucleotide-binding protein G(q) subunit alpha
K05858  phosphatidylinositol phospholipase C, beta [EC:3.1.4.11]
Compound
C00025  L-Glutamate
C00076  Calcium cation
C00165  Diacylglycerol
C00305  Magnesium cation
C00575  3',5'-Cyclic AMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
Reference
  Authors
Blitzer RD, Iyengar R, Landau EM.
  Title
Postsynaptic signaling networks: cellular cogwheels underlying long-term plasticity.
  Journal
Biol Psychiatry 57:113-9 (2005)
DOI:10.1016/j.biopsych.2004.02.031
Reference
  Authors
Soderling TR, Derkach VA.
  Title
Postsynaptic protein phosphorylation and LTP.
  Journal
Trends Neurosci 23:75-80 (2000)
DOI:10.1016/S0166-2236(99)01490-3
Reference
  Authors
Poser S, Storm DR.
  Title
Role of Ca2+-stimulated adenylyl cyclases in LTP and memory formation.
  Journal
Int J Dev Neurosci 19:387-94 (2001)
DOI:10.1016/S0736-5748(00)00094-0
Reference
  Authors
Xia Z, Storm DR.
  Title
The role of calmodulin as a signal integrator for synaptic plasticity.
  Journal
Nat Rev Neurosci 6:267-76 (2005)
DOI:10.1038/nrn1647
Reference
  Authors
Purves D, Augustine GJ (ed).
  Title
Neuroscience
  Journal
Sunderland, Mass.:Sinauer Associates (2004)
Reference
  Authors
Lynch MA.
  Title
Long-term potentiation and memory.
  Journal
Physiol Rev 84:87-136 (2004)
DOI:10.1152/physrev.00014.2003
Reference
  Authors
Kelly PT, Mackinnon RL 2nd, Dietz RV, Maher BJ, Wang J.
  Title
Postsynaptic IP3 receptor-mediated Ca2+ release modulates synaptic transmission in hippocampal neurons.
  Journal
Brain Res Mol Brain Res 135:232-48 (2005)
DOI:10.1016/j.molbrainres.2004.12.018
Reference
PMID:9697848
  Authors
Berridge MJ.
  Title
Neuronal calcium signaling.
  Journal
Neuron 21:13-26 (1998)
DOI:10.1016/S0896-6273(00)80510-3

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