Homeostatic shutdown of long-term potentiation in the adult hippocampus

doi:10.1073/pnas.0600894103

Homeostatic shutdown of long-term potentiation in the adult hippocampus

*Max Planck Institute of Neurobiology, Am Klopferspitz 18, 82152 Martinsried, Germany; and
^†Laboratory for Cognitive Neuroscience, University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, United Kingdom

Edited by Charles F. Stevens, The Salk Institute for Biological Studies, La Jolla, CA, and approved June 5, 2006 (received for review February 6, 2006)

Abstract

Homeostasis is a key concept in biology. It enables ecosystems, organisms, organs, and cells to adjust their operating range to values that ensure optimal performance. Homeostatic regulation of the strength of neuronal connections has been shown to play an important role in the development of the nervous system. Here we investigate whether mature neurons also possess mechanisms to prevent the strengthening of input synapses once the limit of their operating range has been reached. Using electrophysiological recordings in hippocampal slices, we show that such a mechanism exists but comes into play only after a considerable number of synapses have been potentiated. Thus, adult neurons can sustain a substantial amount of synaptic strengthening but, once a certain threshold of potentiation is exceeded, homeostatic regulation ensures that no further strengthening can occur.

Footnotes

^§To whom correspondence should be addressed. E-mail: tobias.bonhoeffer{at}neuro.mpg.de
↵ ^‡Present address: Zoological Institute, Technische Universität Braunschweig, Mendelssohnstrasse 4, 38106 Braunschweig, Germany.
Author contributions: C.R.-A., R.G.M.M., M.K., and T.B. designed research; C.R.-A. performed research; C.R.-A., M.K., and T.B. analyzed data; and C.R.-A., R.G.M.M., M.K., and T.B. wrote the paper.
Conflict of interest statement: No conflicts declared.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations:

Abbreviations:

LTP,

long-term potentiation;

fEPSP,

field excitatory postsynaptic potential.