PSD-95 is required for activity-driven synapse stabilization

doi:10.1073/pnas.0609307104

PSD-95 is required for activity-driven synapse stabilization

Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724

Communicated by Richard L. Huganir, Johns Hopkins University School of Medicine, Baltimore, MD, December 14, 2006 (received for review May 15, 2006)

Abstract

The activity-dependent regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors and the stabilization of synapses are critical to synaptic development and plasticity. One candidate molecule implicated in maturation, synaptic strengthening, and plasticity is PSD-95. Here we find that acute knockdown of PSD-95 in brain slice cultures by RNAi arrests the normal development of synaptic structure and function that is driven by spontaneous activity. Surprisingly, PSD-95 is not necessary for the induction and early expression of long-term potentiation (LTP). However, knockdown of PSD-95 leads to smaller increases in spine size after chemically induced LTP. Furthermore, although at this age spine turnover is normally low and LTP produces a transient increase, in cells with reduced PSD-95 spine turnover is high and remains increased after LTP. Taken together, our data support a model in which appropriate levels of PSD-95 are required for activity-dependent synapse stabilization after initial phases of synaptic potentiation.

Footnotes

*To whom correspondence should be sent at the present address:
Friedrich Miescher Institute, Maulbeerstrasse 66, 4058 Basel, Switzerland
. E-mail: ingrid.ehrlich{at}fmi.ch
Author contributions: I.E. and R.M. designed research; I.E., M.K., and S.R. performed research; I.E. and S.R. analyzed data; and I.E. and R.M. wrote the paper.
↵ ^†Present address: Research Institute of Molecular Pathology, Dr. Bohr-Gasse, A-1030 Vienna, Austria.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/cgi/content/full/0609307104/DC1.
Abbreviations:

EPSC,

excitatory postsynaptic current;

mEPSC,

miniature EPSC;

AMPA,

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid;

LTP,

long-term potentiation;

LTD,

long-term depression;

shRNA,

short hairpin RNA;

Div,

days in vitro;

TOR,

turnover rate;

APV,

2-amino-5-phosphonovaleric acid.