KEGG   PATHWAY: rno04730
Entry
rno04730                    Pathway                                
Name
Long-term depression - Rattus norvegicus (rat)
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
rno04730  Long-term depression
rno04730

Other DBs
GO: 0048169
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
100362453  Ppp2cal1; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform-like [KO:K04382] [EC:3.1.3.16]
114207  Ryr1; ryanodine receptor 1 [KO:K04961]
114486  Braf; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:2.7.11.1]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
117281  Ppp2r1a; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
170851  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
24414  Grm1; metabotropic glutamate receptor 1 isoform alpha precursor [KO:K04603]
24482  Igf1; insulin-like growth factor I isoform d preproprotein [KO:K05459]
24525  Kras; GTPase KRas [KO:K07827]
24598  Nos1; nitric oxide synthase 1 [KO:K13240] [EC:1.14.13.39]
24605  Nras; GTPase NRas [KO:K07828]
24653  Pla2g4a; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
24654  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
24672  Ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
24673  Ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
24680  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
24681  Prkcg; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
24703  Raf1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
24896  Gnas; SCG6 (secretogranin VI) isoform SCG6 precursor [KO:K04632]
25023  Prkcb; protein kinase C beta type isoform 2 [KO:K19662] [EC:2.7.11.13]
25031  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
25202  Gucy1b1; guanylate cyclase soluble subunit beta-1 [KO:K12319] [EC:4.6.1.2]
25206  Gucy1b2; guanylate cyclase soluble subunit beta-2 isoform 2 [KO:K12319] [EC:4.6.1.2]
25262  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform 3 [KO:K04958]
25398  Cacna1a; voltage-dependent P/Q-type calcium channel subunit alpha-1A [KO:K04344]
25523  Prkg2; cGMP-dependent protein kinase 2 [KO:K19477] [EC:2.7.11.12]
25643  Gnai3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
25679  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
25686  Gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
25718  Igf1r; insulin-like growth factor 1 receptor isoform 2 precursor [KO:K05087] [EC:2.7.10.1]
25740  Gnaz; guanine nucleotide-binding protein G(z) subunit alpha [KO:K04535]
266705  Ppp1r17; protein phosphatase 1 regulatory subunit 17 [KO:K08067]
29322  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
293621  Hras; GTPase HRas [KO:K02833]
296091  Pla2g4e; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
29627  Gria2; glutamate receptor 2 isoform 2 precursor [KO:K05198]
29628  Gria3; glutamate receptor 3 isoform 2 precursor [KO:K05199]
303634  Gna13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
311341  Pla2g4b; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
315648  Ppp2r1b; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
367858  Hrasl1; HRas proto-oncogene, GTPase like 1 [KO:K02833]
497757  Gucy1a1; guanylate cyclase soluble subunit alpha-1 [KO:K12318] [EC:4.6.1.2]
50592  Gria1; glutamate receptor 1 precursor [KO:K05197]
50664  Gnao1; guanine nucleotide-binding protein G(o) subunit alpha isoform B [KO:K04534]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
54286  Prkg1; cGMP-dependent protein kinase 1 [KO:K07376] [EC:2.7.11.12]
58959  Crhr1; corticotropin-releasing factor receptor 1 isoform 1 precursor [KO:K04578]
58960  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
64363  Araf; serine/threonine-protein kinase A-Raf isoform 1 [KO:K08845] [EC:2.7.11.1]
66012  Gucy1a2; guanylate cyclase soluble subunit alpha-2 [KO:K12318] [EC:4.6.1.2]
691810  Pla2g4c; cytosolic phospholipase A2 gamma [KO:K16342] [EC:3.1.1.4]
691905  Pla2g4d; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
691907  Pla2g4f; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
79220  Grid2; glutamate receptor ionotropic, delta-2 precursor [KO:K05207]
81515  Lyn; tyrosine-protein kinase Lyn isoform A [KO:K05854] [EC:2.7.10.2]
81648  Crh; corticoliberin precursor [KO:K05256]
81662  Gna11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
81663  Gna12; guanine nucleotide-binding protein subunit alpha-12 [KO:K04346]
81664  Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
81666  Gnaq; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
81678  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
85240  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
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
rno04020  Calcium signaling pathway
rno04724  Glutamatergic synapse
KO pathway
ko04730   

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