Acute restraint stress decreases c-fos immunoreactivity in hilar mossy cells of the adult dentate gyrus

Brain Struct Funct. 2017 Jul;222(5):2405-2419. doi: 10.1007/s00429-016-1349-z. Epub 2017 Feb 11.


Although a great deal of information is available about the circuitry of the mossy cells (MCs) of the dentate gyrus (DG) hilus, their activity in vivo is not clear. The immediate early gene c-fos can be used to gain insight into the activity of MCs in vivo, because c-fos protein expression reflects increased neuronal activity. In prior work, it was identified that control rats that were perfusion-fixed after removal from their home cage exhibited c-fos immunoreactivity (ir) in the DG in a spatially stereotyped pattern: ventral MCs and dorsal granule cells (GCs) expressed c-fos protein (Duffy et al., Hippocampus 23:649-655, 2013). In this study, we hypothesized that restraint stress would alter c-fos-ir, because MCs express glucocorticoid type 2 receptors and the DG is considered to be involved in behaviors related to stress or anxiety. We show that acute restraint using a transparent nose cone for just 10 min led to reduced c-fos-ir in ventral MCs compared to control rats. In these comparisons, c-fos-ir was evaluated 30 min after the 10 min-long period of restraint, and if evaluation was later than 30 min c-fos-ir was no longer suppressed. Granule cells (GCs) also showed suppressed c-fos-ir after acute restraint, but it was different than MCs, because the suppression persisted for over 30 min after the restraint. We conclude that c-fos protein expression is rapidly and transiently reduced in ventral hilar MCs after a brief period of restraint, and suppressed longer in dorsal GCs.

Keywords: Granule cell; Hilus; Hippocampus; Interneuron.

MeSH terms

  • Aging
  • Animals
  • Anxiety / metabolism
  • Cell Count / methods
  • Dentate Gyrus / metabolism*
  • Genes, Immediate-Early / physiology
  • Hippocampus / metabolism*
  • Male
  • Mossy Fibers, Hippocampal / metabolism*
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Rats, Sprague-Dawley
  • Restraint, Physical / methods


  • Proto-Oncogene Proteins c-fos