KEGG   PATHWAY: mmu04730
Entry
mmu04730                    Pathway                                
Name
Long-term depression - Mus musculus (house mouse)
Description
Cerebellar long-term depression (LTD), thought to be a molecular and cellular basis for cerebellar learning, is a process involving a decrease in the synaptic strength between parallel fiber (PF) and Purkinje cells (PCs) induced by the conjunctive activation of PFs and climbing fiber (CF). Multiple signal transduction pathways have been shown to be involved in this process. Activation of PFs terminating on spines in dendritic branchlets leads to glutamate release and activation of both AMPA and mGluRs. Activation of CFs, which make multiple synaptic contacts on proximal dendrites, also via AMPA receptors, opens voltage-gated calcium channels (VGCCs) and causes a generalized influx of calcium. These cellular signals, generated from two different synaptic origins, trigger a cascade of events culminating in a phosphorylation-dependent, long-term reduction in AMPA receptor sensitivity at the PF-PC synapse. This may take place either through receptor internalization and/or through receptor desensitization.
Class
Organismal Systems; Nervous system
Pathway map
mmu04730  Long-term depression
mmu04730

Other DBs
GO: 0048169
Organism
Mus musculus (house mouse) [GN:mmu]
Gene
18125  Nos1; nitric oxide synthase 1, neuronal [KO:K13240] [EC:1.14.13.39]
60596  Gucy1a1; guanylate cyclase 1, soluble, alpha 1 [KO:K12318] [EC:4.6.1.2]
234889  Gucy1a2; guanylate cyclase 1, soluble, alpha 2 [KO:K12318] [EC:4.6.1.2]
239134  Gucy1b2; guanylate cyclase 1, soluble, beta 2 [KO:K12319] [EC:4.6.1.2]
54195  Gucy1b1; guanylate cyclase 1, soluble, beta 1 [KO:K12319] [EC:4.6.1.2]
19091  Prkg1; protein kinase, cGMP-dependent, type I [KO:K07376] [EC:2.7.11.12]
19092  Prkg2; protein kinase, cGMP-dependent, type II [KO:K19477] [EC:2.7.11.12]
19051  Ppp1r17; protein phosphatase 1, regulatory subunit 17 [KO:K08067]
51792  Ppp2r1a; protein phosphatase 2, regulatory subunit A, alpha [KO:K03456]
73699  Ppp2r1b; protein phosphatase 2, regulatory subunit A, beta [KO:K03456]
19052  Ppp2ca; protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform [KO:K04382] [EC:3.1.3.16]
19053  Ppp2cb; protein phosphatase 2 (formerly 2A), catalytic subunit, beta isoform [KO:K04382] [EC:3.1.3.16]
15461  Hras; Harvey rat sarcoma virus oncogene [KO:K02833]
16653  Kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
18176  Nras; neuroblastoma ras oncogene [KO:K07828]
11836  Araf; Araf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
109880  Braf; Braf transforming gene [KO:K04365] [EC:2.7.11.1]
110157  Raf1; v-raf-leukemia viral oncogene 1 [KO:K04366] [EC:2.7.11.1]
26395  Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
26396  Map2k2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
26413  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
26417  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
14804  Grid2; glutamate receptor, ionotropic, delta 2 [KO:K05207]
14816  Grm1; glutamate receptor, metabotropic 1 [KO:K04603]
14677  Gnai1; G protein subunit alpha i1 [KO:K04630]
14679  Gnai3; G protein subunit alpha i3 [KO:K04630]
14678  Gnai2; G protein subunit alpha i2 [KO:K04630]
14681  Gnao1; guanine nucleotide binding protein, alpha O [KO:K04534]
14687  Gnaz; guanine nucleotide binding protein, alpha z subunit [KO:K04535]
14683  Gnas; GNAS complex locus [KO:K04632]
14673  Gna12; guanine nucleotide binding protein, alpha 12 [KO:K04346]
14674  Gna13; guanine nucleotide binding protein, alpha 13 [KO:K04639]
329502  Pla2g4e; phospholipase A2, group IVE [KO:K16342] [EC:3.1.1.4]
18783  Pla2g4a; phospholipase A2, group IVA (cytosolic, calcium-dependent) [KO:K16342] [EC:3.1.1.4]
211429  Pla2g4b; phospholipase A2, group IVB (cytosolic) [KO:K16342] [EC:3.1.1.4]
232889  Pla2g4c; phospholipase A2, group IVC (cytosolic, calcium-independent) [KO:K16342] [EC:3.1.1.4]
78390  Pla2g4d; phospholipase A2, group IVD [KO:K16342] [EC:3.1.1.4]
271844  Pla2g4f; phospholipase A2, group IVF [KO:K16342] [EC:3.1.1.4]
18750  Prkca; protein kinase C, alpha [KO:K02677] [EC:2.7.11.13]
18751  Prkcb; protein kinase C, beta [KO:K19662] [EC:2.7.11.13]
18752  Prkcg; protein kinase C, gamma [KO:K19663] [EC:2.7.11.13]
14682  Gnaq; guanine nucleotide binding protein, alpha q polypeptide [KO:K04634]
14672  Gna11; guanine nucleotide binding protein, alpha 11 [KO:K04635]
18795  Plcb1; phospholipase C, beta 1 [KO:K05858] [EC:3.1.4.11]
18797  Plcb3; phospholipase C, beta 3 [KO:K05858] [EC:3.1.4.11]
18798  Plcb4; phospholipase C, beta 4 [KO:K05858] [EC:3.1.4.11]
18796  Plcb2; phospholipase C, beta 2 [KO:K05858] [EC:3.1.4.11]
14799  Gria1; glutamate receptor, ionotropic, AMPA1 (alpha 1) [KO:K05197]
14800  Gria2; glutamate receptor, ionotropic, AMPA2 (alpha 2) [KO:K05198]
53623  Gria3; glutamate receptor, ionotropic, AMPA3 (alpha 3) [KO:K05199]
17096  Lyn; LYN proto-oncogene, Src family tyrosine kinase [KO:K05854] [EC:2.7.10.2]
12286  Cacna1a; calcium channel, voltage-dependent, P/Q type, alpha 1A subunit [KO:K04344]
16438  Itpr1; inositol 1,4,5-trisphosphate receptor 1 [KO:K04958]
16439  Itpr2; inositol 1,4,5-triphosphate receptor 2 [KO:K04959]
16440  Itpr3; inositol 1,4,5-triphosphate receptor 3 [KO:K04960]
20190  Ryr1; ryanodine receptor 1, skeletal muscle [KO:K04961]
12918  Crh; corticotropin releasing hormone [KO:K05256]
12921  Crhr1; corticotropin releasing hormone receptor 1 [KO:K04578]
16000  Igf1; insulin-like growth factor 1 [KO:K05459]
16001  Igf1r; insulin-like growth factor I receptor [KO:K05087] [EC:2.7.10.1]
Compound
C00025  L-Glutamate
C00076  Calcium cation
C00165  Diacylglycerol
C00219  Arachidonate
C00533  Nitric oxide
C00641  1,2-Diacyl-sn-glycerol
C00942  3',5'-Cyclic GMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
Reference
PMID:12415297
  Authors
Ito M.
  Title
The molecular organization of cerebellar long-term depression.
  Journal
Nat Rev Neurosci 3:896-902 (2002)
DOI:10.1038/nrn962
Reference
PMID:11427694
  Authors
Ito M.
  Title
Cerebellar long-term depression: characterization, signal transduction, and functional roles.
  Journal
Physiol Rev 81:1143-95 (2001)
DOI:10.1152/physrev.2001.81.3.1143
Reference
  Authors
Purves D, Augustine GJ (ed).
  Title
Neuroscience
  Journal
Sunderland, Mass.:Sinauer Associates (2004)
Reference
PMID:9735948
  Authors
Daniel H, Levenes C, Crepel F.
  Title
Cellular mechanisms of cerebellar LTD.
  Journal
Trends Neurosci 21:401-7 (1998)
DOI:10.1016/S0166-2236(98)01304-6
Reference
PMID:9602501
  Authors
Levenes C, Daniel H, Crepel F.
  Title
Long-term depression of synaptic transmission in the cerebellum: cellular and molecular mechanisms revisited.
  Journal
Prog Neurobiol 55:79-91 (1998)
DOI:10.1016/S0301-0082(97)00096-8
Reference
PMID:14509570
  Authors
Metzger F, Kapfhammer JP.
  Title
Protein kinase C: its role in activity-dependent Purkinje cell dendritic development and plasticity.
  Journal
Cerebellum 2:206-14 (2003)
DOI:10.1080/14734220310016150
Related
pathway
mmu04020  Calcium signaling pathway
mmu04724  Glutamatergic synapse
KO pathway
ko04730   
LinkDB

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