Long-term potentiation - Homo sapiens (human)
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).
Organismal Systems; Nervous system
Pathway map Ortholog table
N00984 mGluR5-Ca2+ -apoptotic pathway
Homo sapiens (human) [GN:
2890 GRIA1; glutamate ionotropic receptor AMPA type subunit 1 [KO: K05197]
2891 GRIA2; glutamate ionotropic receptor AMPA type subunit 2 [KO: K05198]
5502 PPP1R1A; protein phosphatase 1 regulatory inhibitor subunit 1A [KO: K08050]
815 CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO: K04515] [EC: 188.8.131.52]
817 CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO: K04515] [EC: 184.108.40.206]
816 CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO: K04515] [EC: 220.127.116.11]
818 CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO: K04515] [EC: 18.104.22.168]
10411 RAPGEF3; Rap guanine nucleotide exchange factor 3 [KO: K08014]
5906 RAP1A; RAP1A, member of RAS oncogene family [KO: K04353]
5908 RAP1B; RAP1B, member of RAS oncogene family [KO: K07836]
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 ionotropic receptor NMDA type subunit 1 [KO: K05208]
2903 GRIN2A; glutamate ionotropic receptor NMDA type subunit 2A [KO: K05209]
2904 GRIN2B; glutamate ionotropic receptor NMDA type subunit 2B [KO: K05210]
2905 GRIN2C; glutamate ionotropic receptor NMDA type subunit 2C [KO: K05211]
2906 GRIN2D; glutamate ionotropic receptor NMDA type subunit 2D [KO: K05212]
775 CACNA1C; calcium voltage-gated channel subunit alpha1 C [KO: K04850]
468 ATF4; activating transcription factor 4 [KO: K04374]
3265 HRAS; HRas proto-oncogene, GTPase [KO: K02833]
3845 KRAS; KRAS proto-oncogene, GTPase [KO: K07827]
4893 NRAS; NRAS proto-oncogene, GTPase [KO: K07828]
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]
2911 GRM1; glutamate metabotropic receptor 1 [KO: K04603]
2915 GRM5; glutamate metabotropic receptor 5 [KO: K04604]
C01245 D-myo-Inositol 1,4,5-trisphosphate
Blitzer RD, Iyengar R, Landau EM.
Postsynaptic signaling networks: cellular cogwheels underlying long-term plasticity.
Soderling TR, Derkach VA.
Postsynaptic protein phosphorylation and LTP.
Poser S, Storm DR.
Role of Ca2+-stimulated adenylyl cyclases in LTP and memory formation.
Xia Z, Storm DR.
The role of calmodulin as a signal integrator for synaptic plasticity.
Purves D, Augustine GJ (ed).
Sunderland, Mass.:Sinauer Associates (2004)
Long-term potentiation and memory.
Kelly PT, Mackinnon RL 2nd, Dietz RV, Maher BJ, Wang J.
Postsynaptic IP3 receptor-mediated Ca2+ release modulates synaptic transmission in hippocampal neurons.
Neuronal calcium signaling.