Synaptopodin regulates denervation-induced homeostatic synaptic plasticity

Proc Natl Acad Sci U S A. 2013 May 14;110(20):8242-7. doi: 10.1073/pnas.1213677110. Epub 2013 Apr 29.


Synaptopodin (SP) is a marker and essential component of the spine apparatus (SA), an enigmatic cellular organelle composed of stacked smooth endoplasmic reticulum that has been linked to synaptic plasticity. However, SP/SA-mediated synaptic plasticity remains incompletely understood. To study the role of SP/SA in homeostatic synaptic plasticity we here used denervation-induced synaptic scaling of mouse dentate granule cells as a model system. This form of plasticity is of considerable interest in the context of neurological diseases that are associated with the loss of neurons and subsequent denervation of connected brain regions. In entorhino-hippocampal slice cultures prepared from SP-deficient mice, which lack the SA, a compensatory increase in excitatory synaptic strength was not observed following partial deafferentation. In line with this finding, prolonged blockade of sodium channels with tetrodotoxin induced homeostatic synaptic scaling in wild-type, but not SP-deficient, slice cultures. By crossing SP-deficient mice with a newly generated transgenic mouse strain that expresses GFP-tagged SP under the control of the Thy1.2 promoter, the ability of dentate granule cells to form the SA and to homeostatically strengthen excitatory synapses was rescued. Interestingly, homeostatic synaptic strengthening was accompanied by a compensatory increase in SP cluster size/stability and SA stack number, suggesting that activity-dependent SP/SA remodeling could be part of a negative feedback mechanism that aims at adjusting the strength of excitatory synapses to persisting changes in network activity. Thus, our results disclose an important role for SP/SA in homeostatic synaptic plasticity.

Keywords: NMDA receptors; entorhinal cortex lesion; intracellular calcium stores; ryanodine receptors; voltage-gated calcium channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels / metabolism
  • Dendritic Spines / metabolism
  • Denervation*
  • Dentate Gyrus / cytology*
  • Entorhinal Cortex / metabolism
  • Green Fluorescent Proteins / metabolism
  • Hippocampus / metabolism
  • Homeostasis
  • In Vitro Techniques
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microfilament Proteins / metabolism*
  • Neuronal Plasticity*
  • Patch-Clamp Techniques
  • Promoter Regions, Genetic
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Ryanodine Receptor Calcium Release Channel / metabolism
  • Synapses / metabolism
  • Tetrodotoxin / pharmacology


  • Calcium Channels
  • Microfilament Proteins
  • Receptors, N-Methyl-D-Aspartate
  • Ryanodine Receptor Calcium Release Channel
  • Synpo protein, mouse
  • Green Fluorescent Proteins
  • Tetrodotoxin