Entry
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
BRITE hierarchy
Pathway map
Other DBs
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 ]
117281 Ppp2r1a; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456 ]
24414 Grm1; metabotropic glutamate receptor 1 isoform alpha precursor [KO:K04603 ]
24482 Igf1; insulin-like growth factor I isoform d preproprotein [KO:K05459 ]
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 ]
24896 Gnas; SCG6 (secretogranin VI) isoform SCG6 precursor [KO:K04632 ]
25031 Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858 ] [EC:3.1.4.11 ]
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 ]
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 ]
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 ]
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 ]
50592 Gria1; glutamate receptor 1 precursor [KO:K05197 ]
50664 Gnao1; guanine nucleotide-binding protein G(o) subunit alpha isoform B [KO:K04534 ]
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 ]
79220 Grid2; glutamate receptor ionotropic, delta-2 precursor [KO:K05207 ]
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
C01245 D-myo-Inositol 1,4,5-trisphosphate
Reference
Authors
Ito M.
Title
The molecular organization of cerebellar long-term depression.
Journal
Reference
Authors
Ito M.
Title
Cerebellar long-term depression: characterization, signal transduction, and functional roles.
Journal
Reference
Authors
Purves D, Augustine GJ (ed).
Title
Neuroscience
Journal
Sunderland, Mass.:Sinauer Associates (2004)
Reference
Authors
Daniel H, Levenes C, Crepel F.
Title
Cellular mechanisms of cerebellar LTD.
Journal
Reference
Authors
Levenes C, Daniel H, Crepel F.
Title
Long-term depression of synaptic transmission in the cerebellum: cellular and molecular mechanisms revisited.
Journal
Reference
Authors
Metzger F, Kapfhammer JP.
Title
Protein kinase C: its role in activity-dependent Purkinje cell dendritic development and plasticity.
Journal
Related pathway
KO pathway