RIM1α is required for presynaptic long-term potentiation

Pablo E. Castillo, Susanne Schoch, Frank Schmitz, Thomas C. Südhof, Robert C. Malenka

Research output: Contribution to journalArticle

296 Citations (Scopus)

Abstract

Two main forms of long-term potentiation (LTP) - a prominent model for the cellular mechanism of learning and memory - have been distinguished in the mammalian brain. One requires activation of postsynaptic NMDA (N-methyl D-aspartate) receptors, whereas the other, called mossy fibre LTP, has a principal presynaptic component. Mossy fibre LTP is expressed in hippocampal mossy fibre synapses, cerebellar parallel fibre synapses and corticothalamic synapses, where it apparently operates by a mechanism that requires activation of protein kinase A. Thus, presynaptic substrates of protein kinase A are probably essential in mediating this form of long-term synaptic plasticity. Studies of knockout mice have shown that the synaptic vesicle protein Rab3A is required for mossy fibre LTP, but the protein kinase A substrates rabphilin, synapsin I and synapsin II are dispensable, Here we report that mossy fibre LTP in the hippocampus and the cerebellum is abolished in mice lacking RIM1α, an active zone protein that binds to Rab3A and that is also a protein kinase A substrate. Our results indicate that the long-term increase in neurotransmitter release during mossy fibre LTP may be mediated by a unitary mechanism that involves the GTP-dependent interaction of Rab3A with RIM1α at the interface of synaptic vesicles and the active zone.

Original languageEnglish (US)
Pages (from-to)327-330
Number of pages4
JournalNature
Volume415
Issue number6869
DOIs
StatePublished - Jan 17 2002

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Long-Term Potentiation
Cyclic AMP-Dependent Protein Kinases
Synapses
Synapsins
Synaptic Vesicles
rab3A GTP-Binding Protein
Hippocampal Mossy Fibers
Neuronal Plasticity
Guanosine Triphosphate
N-Methyl-D-Aspartate Receptors
Knockout Mice
Cerebellum
Neurotransmitter Agents
Hippocampus
Learning
Brain
Proteins

ASJC Scopus subject areas

  • General

Cite this

Castillo, P. E., Schoch, S., Schmitz, F., Südhof, T. C., & Malenka, R. C. (2002). RIM1α is required for presynaptic long-term potentiation. Nature, 415(6869), 327-330. https://doi.org/10.1038/415327a

RIM1α is required for presynaptic long-term potentiation. / Castillo, Pablo E.; Schoch, Susanne; Schmitz, Frank; Südhof, Thomas C.; Malenka, Robert C.

In: Nature, Vol. 415, No. 6869, 17.01.2002, p. 327-330.

Research output: Contribution to journalArticle

Castillo, PE, Schoch, S, Schmitz, F, Südhof, TC & Malenka, RC 2002, 'RIM1α is required for presynaptic long-term potentiation', Nature, vol. 415, no. 6869, pp. 327-330. https://doi.org/10.1038/415327a
Castillo PE, Schoch S, Schmitz F, Südhof TC, Malenka RC. RIM1α is required for presynaptic long-term potentiation. Nature. 2002 Jan 17;415(6869):327-330. https://doi.org/10.1038/415327a
Castillo, Pablo E. ; Schoch, Susanne ; Schmitz, Frank ; Südhof, Thomas C. ; Malenka, Robert C. / RIM1α is required for presynaptic long-term potentiation. In: Nature. 2002 ; Vol. 415, No. 6869. pp. 327-330.
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