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

• DOI: 10.1111/epi.13376
• Publication Date: 2016-03-31T10:52:50Z
• Authors: Gabrielle Hofmann; Laura Balgooyen; Joanna Mattis; Karl Deisseroth; Paul S. Buckmaster
• Keywords: Green Fluorescent Proteins; Pilocarpine; Mice, Transgenic; Neural Inhibition; Muscarinic Agonists; Transfection; Statistics, Nonparametric; Mice, Inbred C57BL; Optogenetics; Disease Models, Animal; Mice; Epilepsy, Temporal Lobe; Interneurons; Dentate Gyrus; Animals; Somatostatin

SummaryObjectiveIn 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.MethodsThe 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.ResultsIn 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.SignificanceThese findings suggest that severe epilepsy‐related loss of hilar somatostatin interneurons can overwhelm the surviving interneurons' capacity to compensate by sprouting axon collaterals.