LTP and adaptation to inactivity: Overlapping mechanisms and implications for metaplasticity

Tara C. Thiagarajan, Maria Lindskog, Antonio Malgaroli, Richard W. Tsien

Research output: Contribution to journalArticlepeer-review

Abstract

LTP and other rapidly induced forms of synaptic modification tune individual synaptic weights, whereas slower forms of plasticity such as adaptation to inactivity are thought to keep neurons within their firing limits and preserve their capability for information processing. Here we describe progress in understanding the relationship between LTP and adaptation to inactivity. A prevailing view is that adaptation to inactivity is purely postsynaptic, scales synaptic strength uniformly across all synapses, and thus preserves relative synaptic weights without interfering with signatures of prior LTP or the relative capacity for future LTP. However, recent evidence in hippocampal neurons indicates that, like LTP, adaptation to AMPA receptor blockade can draw upon a repertoire of synaptic expression mechanisms including enhancement of presynaptic vesicular turnover and increased quantal amplitude mediated by recruitment of homomeric GluR1 AMPA receptors. These pre- and postsynaptic changes appeared coordinated and preferentially expressed at subset of synapses, thereby increasing the variability of miniature EPSCs. In contrast to the NMDA receptor-, Ca2+ entry-dependent induction of LTP, adaptation to inactivity may be mediated by attenuation of voltage-sensitive L-type Ca2+ channel function. The associated intracellular signaling involves elevation of βCaMKII, which in turn downregulates αCaMKII, a key player in LTP. Thus, adaptation to inactivity and LTP are not strictly independent with regard to mechanisms of signaling and expression. Indeed, we and others have found that responses to LTP-inducing stimuli can be sharply altered by prior inactivity, suggesting that the slow adaptation changes the rules of plasticity-an interesting example of "metaplasticity".

Original languageEnglish
Pages (from-to)156-175
Number of pages20
JournalNeuropharmacology
Volume52
Issue number1
DOIs
Publication statusPublished - Jan 2007

Keywords

  • Adaptation to inactivity
  • CaMKII
  • GluR1
  • LTP
  • Metaplasticity
  • Presynaptic release
  • Synaptic homeostasis

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

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