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Interneurons spark seizure-like activity in the entorhinal cortex
Maxime Lévesque1, Rochelle Herrington1, Shabnam Hamidi1
1Montreal Neurological Institute, McGill University, Montréal, QC H3A 2B4, Canada; Department of Neurology & Neurosurgery, McGill University, Montréal, QC H3A 2B4, Canada; Department of Physiology, McGill University, Montréal, QC H3A 2B4, Canada.
Neurobiology of Disease
|January 2, 2016
Summary
Interneurons, not principal cells, are key drivers of epileptiform activity. This study highlights their critical role in generating interictal discharges and transitioning to ictal events in the rat entorhinal cortex.
Area of Science:
- Neuroscience
- Epilepsy Research
- Cellular Electrophysiology
Background:
- Excessive neuronal synchronization underlies epileptiform discharges.
- The specific roles of GABAergic interneurons and glutamatergic principal cells in interictal and ictal events are not fully understood.
Purpose of the Study:
- To investigate the distinct contributions of interneurons and principal cells to 4-aminopyridine-induced interictal and low-voltage fast (LVF) ictal-like discharges.
- To elucidate the cellular mechanisms driving epileptiform synchronization in the rat entorhinal cortex.
Main Methods:
- Utilized tetrode wire recordings in an in vitro rat entorhinal cortex slice preparation.
- Recorded single-unit activity from 90 cells (69 interneurons, 17 principal cells) during induced interictal and LVF ictal discharges.
- Administered 4-aminopyridine to induce epileptiform activity and blocked ionotropic glutamatergic transmission.
Main Results:
- Interneurons were significantly more active during interictal discharges (66.7%) compared to principal cells (35.3%).
- Interneuron activity increased preceding LVF ictal onset, while principal cell activity remained unchanged.
- Both cell types fired intensely during the ictal tonic phase, but only interneurons exhibited phase-locking with LVF activity (5-15Hz).
- Interneuron involvement in interictal discharges persisted even when glutamatergic transmission was blocked.
Conclusions:
- Interneurons play a prominent role in generating interictal discharges.
- Interneurons are crucial for the transition from interictal to LVF ictal activity.
- This study underscores the critical involvement of interneurons in epileptiform synchronization.
