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 (JP16/USP)
D00848  
Dextromethorphan hydrobromide hydrate (JP16)
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  
GRIA1; glutamate receptor, ionotropic, AMPA 1 [KO:K05197]
2891  
GRIA2; glutamate receptor, ionotropic, AMPA 2 [KO:K05198]
107  
ADCY1; adenylate cyclase 1 (brain) [KO:K08041] [EC:4.6.1.1]
114  
ADCY8; adenylate cyclase 8 (brain) [KO:K08048] [EC:4.6.1.1]
5566  
PRKACA; protein kinase, cAMP-dependent, catalytic, alpha [KO:K04345] [EC:2.7.11.11]
5567  
PRKACB; protein kinase, cAMP-dependent, catalytic, beta [KO:K04345] [EC:2.7.11.11]
5568  
PRKACG; protein kinase, cAMP-dependent, catalytic, gamma [KO:K04345] [EC:2.7.11.11]
5613  
PRKX; protein kinase, X-linked [KO:K04345] [EC:2.7.11.11]
5502  
PPP1R1A; protein phosphatase 1, regulatory (inhibitor) subunit 1A [KO:K08050]
5499  
PPP1CA; protein phosphatase 1, catalytic subunit, alpha isozyme [KO:K06269] [EC:3.1.3.16]
5500  
PPP1CB; protein phosphatase 1, catalytic subunit, beta isozyme [KO:K06269] [EC:3.1.3.16]
5501  
PPP1CC; protein phosphatase 1, catalytic subunit, gamma isozyme [KO:K06269] [EC:3.1.3.16]
815  
CAMK2A; calcium/calmodulin-dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
817  
CAMK2D; calcium/calmodulin-dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
816  
CAMK2B; calcium/calmodulin-dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
818  
CAMK2G; calcium/calmodulin-dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
10411  
RAPGEF3; Rap guanine nucleotide exchange factor (GEF) 3 [KO:K08014]
5906  
RAP1A; RAP1A, member of RAS oncogene family [KO:K04353]
5908  
RAP1B; RAP1B, member of RAS oncogene family [KO:K07836]
5530  
PPP3CA; protein phosphatase 3, catalytic subunit, alpha isozyme [KO:K04348] [EC:3.1.3.16]
5532  
PPP3CB; protein phosphatase 3, catalytic subunit, beta isozyme [KO:K04348] [EC:3.1.3.16]
5533  
PPP3CC; protein phosphatase 3, catalytic subunit, gamma isozyme [KO:K04348] [EC:3.1.3.16]
5534  
PPP3R1; protein phosphatase 3, regulatory subunit B, alpha [KO:K06268]
5535  
PPP3R2; protein phosphatase 3, regulatory subunit B, beta [KO:K06268]
2902  
GRIN1; glutamate receptor, ionotropic, N-methyl D-aspartate 1 [KO:K05208]
2903  
GRIN2A; glutamate receptor, ionotropic, N-methyl D-aspartate 2A [KO:K05209]
2904  
GRIN2B; glutamate receptor, ionotropic, N-methyl D-aspartate 2B [KO:K05210]
2905  
GRIN2C; glutamate receptor, ionotropic, N-methyl D-aspartate 2C [KO:K05211]
2906  
GRIN2D; glutamate receptor, ionotropic, N-methyl D-aspartate 2D [KO:K05212]
775  
CACNA1C; calcium channel, voltage-dependent, L type, alpha 1C subunit [KO:K04850]
810  
CALML3; calmodulin-like 3 [KO:K02183]
805  
CALM2; calmodulin 2 (phosphorylase kinase, delta) [KO:K02183]
808  
CALM3; calmodulin 3 (phosphorylase kinase, delta) [KO:K02183]
801  
CALM1; calmodulin 1 (phosphorylase kinase, delta) [KO:K02183]
163688  
CALML6; calmodulin-like 6 [KO:K02183]
51806  
CALML5; calmodulin-like 5 [KO:K02183]
1387  
CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
2033  
EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
468  
ATF4; activating transcription factor 4 [KO:K04374]
814  
CAMK4; calcium/calmodulin-dependent protein kinase IV [KO:K05869] [EC:2.7.11.17]
3265  
HRAS; Harvey rat sarcoma viral oncogene homolog [KO:K02833]
3845  
KRAS; Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
4893  
NRAS; neuroblastoma RAS viral (v-ras) oncogene homolog [KO:K07828]
369  
ARAF; v-raf murine sarcoma 3611 viral oncogene homolog [KO:K08845] [EC:2.7.11.1]
673  
BRAF; v-raf murine sarcoma viral oncogene homolog B [KO:K04365] [EC:2.7.11.1]
5894  
RAF1; v-raf-1 murine leukemia viral oncogene homolog 1 [KO:K04366] [EC:2.7.11.1]
5604  
MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5605  
MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
5594  
MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  
MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
6197  
RPS6KA3; ribosomal protein S6 kinase, 90kDa, polypeptide 3 [KO:K04373] [EC:2.7.11.1]
6195  
RPS6KA1; ribosomal protein S6 kinase, 90kDa, polypeptide 1 [KO:K04373] [EC:2.7.11.1]
6196  
RPS6KA2; ribosomal protein S6 kinase, 90kDa, polypeptide 2 [KO:K04373] [EC:2.7.11.1]
27330  
RPS6KA6; ribosomal protein S6 kinase, 90kDa, polypeptide 6 [KO:K04373] [EC:2.7.11.1]
3708  
ITPR1; inositol 1,4,5-trisphosphate receptor, type 1 [KO:K04958]
3709  
ITPR2; inositol 1,4,5-trisphosphate receptor, type 2 [KO:K04959]
3710  
ITPR3; inositol 1,4,5-trisphosphate receptor, type 3 [KO:K04960]
5578  
PRKCA; protein kinase C, alpha [KO:K02677] [EC:2.7.11.13]
5579  
PRKCB; protein kinase C, beta [KO:K02677] [EC:2.7.11.13]
5582  
PRKCG; protein kinase C, gamma [KO:K02677] [EC:2.7.11.13]
2911  
GRM1; glutamate receptor, metabotropic 1 [KO:K04603]
2915  
GRM5; glutamate receptor, metabotropic 5 [KO:K04604]
2776  
GNAQ; guanine nucleotide binding protein (G protein), q polypeptide [KO:K04634]
23236  
PLCB1; phospholipase C, beta 1 (phosphoinositide-specific) [KO:K05858] [EC:3.1.4.11]
5330  
PLCB2; phospholipase C, beta 2 [KO:K05858] [EC:3.1.4.11]
5331  
PLCB3; phospholipase C, beta 3 (phosphatidylinositol-specific) [KO:K05858] [EC:3.1.4.11]
5332  
PLCB4; 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
 

DBGET integrated database retrieval system