The sparse activity of hippocampal dentate gyrus (DG) granule cells (GCs) is thought to be critical for cognition and behavior, whereas excessive DG activity may contribute to disorders such as temporal lobe epilepsy (TLE). Glutamatergic mossy cells (MCs) of the DG are potentially critical to normal and pathological functions of the DG because they can regulate GC activity through innervation of GCs or indirectly through GABAergic neurons. Here, we test the hypothesis that MC excitation of GCs is normally weak, but under pathological conditions, MC excitation of GCs is dramatically strengthened. We show that selectively inhibiting MCs during severe seizures reduced manifestations of those seizures, hippocampal injury, and chronic epilepsy. In contrast, selectively activating MCs was pro-convulsant. Mechanistic in vitro studies using optogenetics further demonstrated the unanticipated ability of MC axons to excite GCs under pathological conditions. These results demonstrate an excitatory and epileptogenic effect of MCs in the DG.
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| http://dx.doi.org/10.1016/j.celrep.2019.10.100 | DOI Listing |
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Article Synopsis
- Gamma oscillation regularity (GOR) reflects the synchronization of inhibitory interneurons, while cortico-cortical evoked potentials (CCEPs) indicate local cortical excitability, particularly related to excitatory pyramidal cells.
- In a study involving five patients with mesial temporal lobe epilepsy (MTLE) who had intracranial electrodes implanted, researchers quantified GOR and CCEP responses near stimulation sites to visualize inhibitory and excitatory cortical activities, finding higher activity levels in epileptogenic regions.
- By combining GOR and CCEP data, a new metric called the excitatory and inhibitory (EI) index was developed, which improved specificity in predicting the epileptogenic zone compared to using GOR or CCEP alone,
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