KEGG   PATHWAY: ko04730Help
Entry
ko04730                     Pathway                                

Name
Long-term depression
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
BRITE hierarchy
Pathway map
ko04730  Long-term depression
ko04730

Ortholog table
Disease
H00063  Spinocerebellar ataxia (SCA)
H00699  Central core disease
H00749  Episodic ataxias
H00775  Familial or sporadic hemiplegic migraine
H00833  Neurodegeneration with brain iron accumulation (NBIA)
H01274  Growth delay due to insulin-like growth factor I resistance
H01310  Multi-minicore disease (MmD)
Other DBs
BSID: 497
GO: 0048169
Orthology
K13240  nitric-oxide synthase, brain [EC:1.14.13.39]
K12318  guanylate cyclase soluble subunit alpha [EC:4.6.1.2]
K12319  guanylate cyclase soluble subunit beta [EC:4.6.1.2]
K07376  cGMP-dependent protein kinase 1 [EC:2.7.11.12]
K19477  cGMP-dependent protein kinase 2 [EC:2.7.11.12]
K08067  protein phosphatase 1 regulatory subunit 17
K03456  serine/threonine-protein phosphatase 2A regulatory subunit A
K04382  serine/threonine-protein phosphatase 2A catalytic subunit [EC:3.1.3.16]
K02833  GTPase HRas
K07827  GTPase KRas
K07828  GTPase NRas
K08845  A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04365  B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04366  RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369  mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04371  mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K05207  glutamate receptor delta-2 subunit
K04603  metabotropic glutamate receptor 1
K04630  guanine nucleotide-binding protein G(i) subunit alpha
K04534  guanine nucleotide-binding protein G(o) subunit alpha
K04535  guanine nucleotide-binding protein G(z) subunit alpha
K04632  guanine nucleotide-binding protein G(s) subunit alpha
K04346  guanine nucleotide-binding protein subunit alpha-12
K04639  guanine nucleotide-binding protein subunit alpha-13
K16342  cytosolic phospholipase A2 [EC:3.1.1.4]
K02677  classical protein kinase C alpha type [EC:2.7.11.13]
K19662  classical protein kinase C beta type [EC:2.7.11.13]
K19663  classical protein kinase C gamma type [EC:2.7.11.13]
K04634  guanine nucleotide-binding protein G(q) subunit alpha
K04635  guanine nucleotide-binding protein subunit alpha-11
K05858  phosphatidylinositol phospholipase C, beta [EC:3.1.4.11]
K05197  glutamate receptor 1
K05198  glutamate receptor 2
K05199  glutamate receptor 3
K05854  tyrosine-protein kinase Lyn [EC:2.7.10.2]
K04344  voltage-dependent calcium channel P/Q type alpha-1A
K04958  inositol 1,4,5-triphosphate receptor type 1
K04959  inositol 1,4,5-triphosphate receptor type 2
K04960  inositol 1,4,5-triphosphate receptor type 3
K04961  ryanodine receptor 1
K05256  corticotropin-releasing hormone
K04578  corticotropin releasing hormone receptor 1
K05459  insulin-like growth factor 1
K05087  insulin-like growth factor 1 receptor [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
  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
  Authors
Ito M.
  Title
Cerebellar long-term depression: characterization, signal transduction, and functional roles.
  Journal
Physiol Rev 81:1143-95 (2001)
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
  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

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