KEGG   PATHWAY: hsa04720Help
Entry
hsa04720                    Pathway                                

Name
Long-term potentiation - Homo sapiens (human)
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
Long-term potentiation
hsa04720

All organismsOrtholog table
Drug
D00537  
Topiramate (JAN/USAN/INN)
D00777  
Amantadine hydrochloride (JP17/USP)
D00848  
Dextromethorphan hydrobromide (USP)
D02102  
Methadone hydrochloride (JAN/USP)
D02410  
Selfotel (USAN/INN)
D02696  
Talampanel (INN)
D02973  
Aptiganel hydrochloride (USAN)
D03100  
Besonprodil (USAN)
D03679  
Delucemine hydrochloride (USAN)
D03742  
Dextromethorphan (USP)
D03744  
Dextromethorphan polistirex (USAN)
D03746  
Dextrorphan hydrochloride (USAN)
D03878  
Dizocilpine maleate (USAN)
D04155  
Fenobam (USAN)
D04308  
Gavestinel (USAN/INN)
D04728  
Licostinel (USAN/INN)
D05145  
Neramexane mesylate (USAN)
D05447  
Perzinfotel (USAN/INN)
D05453  
Phencyclidine hydrochloride (USAN)
D05714  
Remacemide hydrochloride (USAN)
D06204  
Traxoprodil mesylate (USAN)
D07441  
Amantadine (INN)
D08121  
Levomethadone (INN)
D08122  
Levomethadone hydrochloride
D08195  
Methadone (BAN)
Other DBs
BSID: 
GO: 
Organism
Homo sapiens (human) [GN:hsa]
Gene
2890  
K05197 glutamate receptor 1 | (RefSeq) GRIA1; glutamate ionotropic receptor AMPA type subunit 1 [KO:K05197]
2891  
K05198 glutamate receptor 2 | (RefSeq) GRIA2; glutamate ionotropic receptor AMPA type subunit 2 [KO:K05198]
107  
K08041 adenylate cyclase 1 [EC:4.6.1.1] | (RefSeq) ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
114  
K08048 adenylate cyclase 8 [EC:4.6.1.1] | (RefSeq) ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
5566  
K04345 protein kinase A [EC:2.7.11.11] | (RefSeq) PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
5567  
K04345 protein kinase A [EC:2.7.11.11] | (RefSeq) PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
5568  
K04345 protein kinase A [EC:2.7.11.11] | (RefSeq) PRKACG; protein kinase cAMP-activated catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
5502  
K08050 protein phosphatase 1 regulatory subunit 1A | (RefSeq) PPP1R1A; protein phosphatase 1 regulatory inhibitor subunit 1A [KO:K08050]
5499  
K06269 serine/threonine-protein phosphatase PP1 catalytic subunit [EC:3.1.3.16] | (RefSeq) PPP1CA; protein phosphatase 1 catalytic subunit alpha [KO:K06269] [EC:3.1.3.16]
5500  
K06269 serine/threonine-protein phosphatase PP1 catalytic subunit [EC:3.1.3.16] | (RefSeq) PPP1CB; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
5501  
K06269 serine/threonine-protein phosphatase PP1 catalytic subunit [EC:3.1.3.16] | (RefSeq) PPP1CC; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
815  
K04515 calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17] | (RefSeq) CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
817  
K04515 calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17] | (RefSeq) CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
816  
K04515 calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17] | (RefSeq) CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
818  
K04515 calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17] | (RefSeq) CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
10411  
K08014 Rap guanine nucleotide exchange factor 3 | (RefSeq) RAPGEF3; Rap guanine nucleotide exchange factor 3 [KO:K08014]
5906  
K04353 Ras-related protein Rap-1A | (RefSeq) RAP1A; RAP1A, member of RAS oncogene family [KO:K04353]
5908  
K07836 Ras-related protein Rap-1B | (RefSeq) RAP1B; RAP1B, member of RAS oncogene family [KO:K07836]
5530  
K04348 serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16] | (RefSeq) PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
5532  
K04348 serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16] | (RefSeq) PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:3.1.3.16]
5533  
K04348 serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16] | (RefSeq) PPP3CC; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:3.1.3.16]
5534  
K06268 serine/threonine-protein phosphatase 2B regulatory subunit | (RefSeq) PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268]
5535  
K06268 serine/threonine-protein phosphatase 2B regulatory subunit | (RefSeq) PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268]
2902  
K05208 glutamate receptor ionotropic; glutamate ionotropic receptor NMDA type subunit 1 [KO:K05208]
2903  
K05209 glutamate receptor ionotropic; glutamate ionotropic receptor NMDA type subunit 2A [KO:K05209]
2904  
K05210 glutamate receptor ionotropic; glutamate ionotropic receptor NMDA type subunit 2B [KO:K05210]
2905  
K05211 glutamate receptor ionotropic; glutamate ionotropic receptor NMDA type subunit 2C [KO:K05211]
2906  
K05212 glutamate receptor ionotropic; glutamate ionotropic receptor NMDA type subunit 2D [KO:K05212]
775  
K04850 voltage-dependent calcium channel L type alpha-1C | (RefSeq) CACNA1C; calcium voltage-gated channel subunit alpha1 C [KO:K04850]
810  
K02183 calmodulin | (RefSeq) CALML3; calmodulin like 3 [KO:K02183]
805  
K02183 calmodulin | (RefSeq) CALM2; calmodulin 2 [KO:K02183]
808  
K02183 calmodulin | (RefSeq) CALM3; calmodulin 3 [KO:K02183]
801  
K02183 calmodulin | (RefSeq) CALM1; calmodulin 1 [KO:K02183]
163688  
K02183 calmodulin | (RefSeq) CALML6; calmodulin like 6 [KO:K02183]
51806  
K02183 calmodulin | (RefSeq) CALML5; calmodulin like 5 [KO:K02183]
91860  
K02183 calmodulin | (RefSeq) CALML4; calmodulin like 4 [KO:K02183]
1387  
K04498 E1A/CREB-binding protein [EC:2.3.1.48] | (RefSeq) CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
2033  
K04498 E1A/CREB-binding protein [EC:2.3.1.48] | (RefSeq) EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
468  
K04374 cyclic AMP-dependent transcription factor ATF-4 | (RefSeq) ATF4; activating transcription factor 4 [KO:K04374]
814  
K05869 calcium/calmodulin-dependent protein kinase IV [EC:2.7.11.17] | (RefSeq) CAMK4; calcium/calmodulin dependent protein kinase IV [KO:K05869] [EC:2.7.11.17]
3265  
K02833 GTPase HRas | (RefSeq) HRAS; HRas proto-oncogene, GTPase [KO:K02833]
3845  
K07827 GTPase KRas | (RefSeq) KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
4893  
K07828 GTPase NRas | (RefSeq) NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
369  
K08845 A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1] | (RefSeq) ARAF; A-Raf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
673  
K04365 B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1] | (RefSeq) BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
5894  
K04366 RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1] | (RefSeq) RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
5604  
K04368 mitogen-activated protein kinase kinase 1 [EC:2.7.12.2] | (RefSeq) MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5605  
K04369 mitogen-activated protein kinase kinase 2 [EC:2.7.12.2] | (RefSeq) MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
5594  
K04371 mitogen-activated protein kinase 1/3 [EC:2.7.11.24] | (RefSeq) MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  
K04371 mitogen-activated protein kinase 1/3 [EC:2.7.11.24] | (RefSeq) MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
6197  
K04373 ribosomal protein S6 kinase alpha-1/2/3/6 [EC:2.7.11.1] | (RefSeq) RPS6KA3; ribosomal protein S6 kinase A3 [KO:K04373] [EC:2.7.11.1]
6195  
K04373 ribosomal protein S6 kinase alpha-1/2/3/6 [EC:2.7.11.1] | (RefSeq) RPS6KA1; ribosomal protein S6 kinase A1 [KO:K04373] [EC:2.7.11.1]
6196  
K04373 ribosomal protein S6 kinase alpha-1/2/3/6 [EC:2.7.11.1] | (RefSeq) RPS6KA2; ribosomal protein S6 kinase A2 [KO:K04373] [EC:2.7.11.1]
27330  
K04373 ribosomal protein S6 kinase alpha-1/2/3/6 [EC:2.7.11.1] | (RefSeq) RPS6KA6; ribosomal protein S6 kinase A6 [KO:K04373] [EC:2.7.11.1]
3708  
K04958 inositol 1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
3709  
K04959 inositol 1; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
3710  
K04960 inositol 1; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
5578  
K02677 classical protein kinase C alpha type [EC:2.7.11.13] | (RefSeq) PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
5579  
K19662 classical protein kinase C beta type [EC:2.7.11.13] | (RefSeq) PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
5582  
K19663 classical protein kinase C gamma type [EC:2.7.11.13] | (RefSeq) PRKCG; protein kinase C gamma [KO:K19663] [EC:2.7.11.13]
2911  
K04603 metabotropic glutamate receptor 1 | (RefSeq) GRM1; glutamate metabotropic receptor 1 [KO:K04603]
2915  
K04604 metabotropic glutamate receptor 5 | (RefSeq) GRM5; glutamate metabotropic receptor 5 [KO:K04604]
2776  
K04634 guanine nucleotide-binding protein G(q) subunit alpha | (RefSeq) GNAQ; G protein subunit alpha q [KO:K04634]
23236  
K05858 phosphatidylinositol phospholipase C; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
5330  
K05858 phosphatidylinositol phospholipase C; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
5331  
K05858 phosphatidylinositol phospholipase C; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
5332  
K05858 phosphatidylinositol phospholipase C; phospholipase C beta 4 [KO:K05858] [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)
Reference
  Authors
Soderling TR, Derkach VA.
  Title
Postsynaptic protein phosphorylation and LTP.
  Journal
Trends Neurosci 23:75-80 (2000)
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)
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)
Reference
  Authors
Purves D, Augustine GJ (ed).
  Title
Neuroscience
  Journal
Sunderland, Mass.:Sinauer Associates (2004)
Reference
(Japanese)
  Authors
Futai K, Hayashi Y.
  Title
[Molecular mechanisms of hippocampal long-term potentiation.] (In Japanese)
  Journal
Experimental Medicine 21(17):2361-2369 (2003)
Reference
  Authors
Lynch MA.
  Title
Long-term potentiation and memory.
  Journal
Physiol Rev 84:87-136 (2004)
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)
Reference
PMID:9697848
  Authors
Berridge MJ.
  Title
Neuronal calcium signaling.
  Journal
Neuron 21:13-26 (1998)
KO pathway
 

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