Granule Cell Ensembles in Mouse Dentate Gyrus Rapidly Upregulate the Plasticity-Related Protein Synaptopodin after Exploration Behavior

Cereb Cortex. 2020 Apr 14;30(4):2185-2198. doi: 10.1093/cercor/bhz231.


The plasticity-related protein Synaptopodin (SP) has been implicated in neuronal plasticity. SP is targeted to dendritic spines and the axon initial segment, where it organizes the endoplasmic reticulum (ER) into the spine apparatus and the cisternal organelle, respectively. Here, we report an inducible third localization of SP in the somata of activated granule cell ensembles in mouse dentate gyrus. Using immunofluorescence and fluorescence in situ hybridization, we observed a subpopulation of mature granule cells (~1-2%) exhibiting perinuclear SP protein and a strong somatic SP mRNA signal. Double immunofluorescence labeling for Arc demonstrated that ~ 75% of these somatic SP-positive cells are also Arc-positive. Placement of mice into a novel environment caused a rapid (~2-4 h) induction of Arc, SP mRNA, and SP protein in exploration-induced granule cell ensembles. Lesion experiments showed that this induction requires input from the entorhinal cortex. Somatic SP colocalized with α-Actinin2, a known binding partner of SP. Finally, ultrastructural analysis revealed SP immunoprecipitate on dense plates linking cytoplasmic and perinuclear ER cisterns; these structures were absent in granule cells of SP-deficient mice. Our data implicate SP in the formation of contextual representations in the dentate gyrus and the behaviorally induced reorganization of cytoplasmic and perinuclear ER.

Keywords: Arc; endoplasmic reticulum; entorhinal cortex lesion; hippocampus; learning and memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dentate Gyrus / cytology*
  • Dentate Gyrus / metabolism*
  • Dentate Gyrus / ultrastructure
  • Exploratory Behavior / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microfilament Proteins / biosynthesis*
  • Microfilament Proteins / deficiency
  • Neuronal Plasticity / physiology*
  • Up-Regulation / physiology*


  • Microfilament Proteins
  • Synpo protein, mouse