KEGG   PATHWAY: ko04720
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
Pathway map
ko04720  Long-term potentiation
ko04720

Other DBs
GO: 0048169
Orthology
K02183  CALM; calmodulin
K02677  PRKCA; classical protein kinase C alpha type [EC:2.7.11.13]
K02833  HRAS; GTPase HRas
K04345  PKA; protein kinase A [EC:2.7.11.11]
K04348  PPP3C, CNA; serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16]
K04353  RAP1A; Ras-related protein Rap-1A
K04365  BRAF; B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04366  RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369  MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04371  ERK, MAPK1_3; mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04373  RPS6KA; ribosomal protein S6 kinase alpha-1/2/3/6 [EC:2.7.11.1]
K04374  ATF4, CREB2; cyclic AMP-dependent transcription factor ATF-4
K04498  EP300, CREBBP, KAT3; E1A/CREB-binding protein [EC:2.3.1.48]
K04515  CAMK2; calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17]
K04603  GRM1; metabotropic glutamate receptor 1
K04604  GRM5; metabotropic glutamate receptor 5
K04634  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha
K04850  CACNA1C, CAV1.2; voltage-dependent calcium channel L type alpha-1C
K04958  ITPR1; inositol 1,4,5-triphosphate receptor type 1
K04959  ITPR2; inositol 1,4,5-triphosphate receptor type 2
K04960  ITPR3; inositol 1,4,5-triphosphate receptor type 3
K05197  GRIA1; glutamate receptor 1
K05198  GRIA2; glutamate receptor 2
K05208  GRIN1; glutamate receptor ionotropic, NMDA 1
K05209  GRIN2A; glutamate receptor ionotropic, NMDA 2A
K05210  GRIN2B; glutamate receptor ionotropic, NMDA 2B
K05211  GRIN2C; glutamate receptor ionotropic, NMDA 2C
K05212  GRIN2D; glutamate receptor ionotropic, NMDA 2D
K05858  PLCB; phosphatidylinositol phospholipase C, beta [EC:3.1.4.11]
K05869  CAMK4; calcium/calmodulin-dependent protein kinase IV [EC:2.7.11.17]
K06268  PPP3R, CNB; serine/threonine-protein phosphatase 2B regulatory subunit
K06269  PPP1C; serine/threonine-protein phosphatase PP1 catalytic subunit [EC:3.1.3.16]
K07827  KRAS, KRAS2; GTPase KRas
K07828  NRAS; GTPase NRas
K07836  RAP1B; Ras-related protein Rap-1B
K08014  RAPGEF3, EPAC1; Rap guanine nucleotide exchange factor 3
K08041  ADCY1; adenylate cyclase 1 [EC:4.6.1.1]
K08048  ADCY8; adenylate cyclase 8 [EC:4.6.1.1]
K08050  PPP1R1A; protein phosphatase 1 regulatory subunit 1A
K08845  ARAF, ARAF1; A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K19662  PRKCB; classical protein kinase C beta type [EC:2.7.11.13]
K19663  PRKCG; classical protein kinase C gamma type [EC:2.7.11.13]
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
PMID:15652868
  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
PMID:10652548
  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
PMID:11378299
  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
PMID:15803158
  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
PMID:14715912
  Authors
Lynch MA.
  Title
Long-term potentiation and memory.
  Journal
Physiol Rev 84:87-136 (2004)
DOI:10.1152/physrev.00014.2003
Reference
PMID:15857686
  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
Related
pathway
ko04010  MAPK signaling pathway
ko04020  Calcium signaling pathway
ko04724  Glutamatergic synapse

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