Hilar somatostatin interneuron loss reduces dentate gyrus inhibition in a mouse model of temporal lobe epilepsy

Epilepsia. 2016 Jun;57(6):977-83. doi: 10.1111/epi.13376. Epub 2016 Mar 31.


Objective: In patients with temporal lobe epilepsy, seizures usually start in the hippocampus, and dentate granule cells are hyperexcitable. Somatostatin interneurons are a major subpopulation of inhibitory neurons in the dentate gyrus, and many are lost in patients and animal models. However, surviving somatostatin interneurons sprout axon collaterals and form new synapses, so the net effect on granule cell inhibition remains unclear.

Methods: The present study uses optogenetics to activate hilar somatostatin interneurons and measure the inhibitory effect on dentate gyrus perforant path-evoked local field potential responses in a mouse model of temporal lobe epilepsy.

Results: In controls, light activation of hilar somatostatin interneurons inhibited evoked responses up to 40%. Epileptic pilocarpine-treated mice exhibited loss of hilar somatostatin interneurons and less light-induced inhibition of evoked responses.

Significance: These findings suggest that severe epilepsy-related loss of hilar somatostatin interneurons can overwhelm the surviving interneurons' capacity to compensate by sprouting axon collaterals.

Keywords: C57BL/6J mice; Channelrhodopsin; Dentate gyrus; Hippocampus; Local field potential; Optogenetics; Perforant path; Pilocarpine.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Dentate Gyrus / pathology*
  • Disease Models, Animal
  • Epilepsy, Temporal Lobe / chemically induced
  • Epilepsy, Temporal Lobe / genetics
  • Epilepsy, Temporal Lobe / pathology*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Interneurons / drug effects
  • Interneurons / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Muscarinic Agonists / toxicity
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Optogenetics
  • Pilocarpine / toxicity
  • Somatostatin / genetics
  • Somatostatin / metabolism*
  • Statistics, Nonparametric
  • Transfection


  • Muscarinic Agonists
  • Pilocarpine
  • Green Fluorescent Proteins
  • Somatostatin