Long lasting protein synthesis- and activity-dependent spine shrinkage and elimination after synaptic depression

PLoS One. 2013 Aug 9;8(8):e71155. doi: 10.1371/journal.pone.0071155. eCollection 2013.

Abstract

Neuronal circuits modify their response to synaptic inputs in an experience-dependent fashion. Increases in synaptic weights are accompanied by structural modifications, and activity dependent, long lasting growth of dendritic spines requires new protein synthesis. When multiple spines are potentiated within a dendritic domain, they show dynamic structural plasticity changes, indicating that spines can undergo bidirectional physical modifications. However, it is unclear whether protein synthesis dependent synaptic depression leads to long lasting structural changes. Here, we investigate the structural correlates of protein synthesis dependent long-term depression (LTD) mediated by metabotropic glutamate receptors (mGluRs) through two-photon imaging of dendritic spines on hippocampal pyramidal neurons. We find that induction of mGluR-LTD leads to robust and long lasting spine shrinkage and elimination that lasts for up to 24 hours. These effects depend on signaling through group I mGluRs, require protein synthesis, and activity. These data reveal a mechanism for long lasting remodeling of synaptic inputs, and offer potential insights into mental retardation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cycloheximide / pharmacology
  • Dendritic Spines / drug effects
  • Dendritic Spines / metabolism*
  • Dendritic Spines / ultrastructure
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Glycine / analogs & derivatives
  • Glycine / pharmacology
  • Long-Term Synaptic Depression / drug effects*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Imaging
  • Patch-Clamp Techniques
  • Protein Biosynthesis / drug effects
  • Pyramidal Cells / cytology
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / metabolism*
  • Receptors, Metabotropic Glutamate / agonists
  • Receptors, Metabotropic Glutamate / metabolism*
  • Resorcinols / pharmacology
  • Synapses / drug effects
  • Synapses / physiology*
  • Synaptic Transmission / drug effects
  • Tissue Culture Techniques

Substances

  • Receptors, Metabotropic Glutamate
  • Resorcinols
  • 3,5-dihydroxyphenylglycine
  • Cycloheximide
  • Glycine

Grants and funding

This work was supported by the Champalimaud Foundation, Gulbenkian Foundation, Bial Foundation, Fundação para Ciência e Tecnologia, and CONACyT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.