Send to:

Choose Destination
See comment in PubMed Commons below
Proc Natl Acad Sci U S A. 2004 Jan 13;101(2):676-81. Epub 2003 Dec 29.

Protein phosphatase 2A inhibition induces cerebellar long-term depression and declustering of synaptic AMPA receptor.

Author information

  • 1Laboratory for Memory and Learning, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.


Phosphorylation of synaptic (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) (AMPA) receptors (AMPARs) is an essential component of cerebellar long-term depression (LTD), a form of synaptic plasticity involved in motor learning. Here, we report that protein phosphatase 2A (PP-2A) plays a specific role in controlling synaptic strength and clustering of AMPARs at synapses between granule cells and Purkinje cells. In 22- to 35-day cerebellar cultures, specific inhibition of postsynaptic PP-2A by fostriecin (100 nM) or cytostatin (10-60 microM) induced a gradual and use-dependent decrease of synaptic current evoked by the stimulation of a single granule cell, without altering receptor kinetics nor passive electrical properties. By contrast, PP-2A inhibition had no effect on immature Purkinje cells (12-15 days). Concurrent PP-2A inhibition and AMPAR stimulation induced a reduction of miniature synaptic currents and a reduction of AMPAR density at synapses. Either PP-2A inhibitor alone or AMPA stimulation alone had no significant effect. Inhibition of PP-1 by inhibitor 1 (10-27 units/microl) had no effect on synaptic current. Synaptic depression induced by PP-2A inhibition occluded subsequent induction of LTD by conjunctive stimulation and was abolished by a calcium chelator or a protein kinase inhibitor, suggesting a shared molecular pathway and involvement of PP-2A in LTD induction.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk