Net synaptic drive of fast-spiking interneurons is inverted towards inhibition in human FCD I epilepsy

Eunhye Cho, Jii Kwon, Gyuwon Lee, Jiwoo Shin, Hyunsu Lee, Suk-Ho Lee, Chun Kee Chung (), Jaeyoung Yoon () and Won-Kyung Ho ()
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Eunhye Cho: Seoul National University College of Medicine
Jii Kwon: Seoul National University College of Natural Sciences
Gyuwon Lee: Seoul National University College of Natural Sciences
Jiwoo Shin: Seoul National University College of Medicine
Hyunsu Lee: Pusan National University School of Medicine
Suk-Ho Lee: Seoul National University College of Medicine
Chun Kee Chung: Seoul National University Hospital
Jaeyoung Yoon: Seoul National University College of Medicine
Won-Kyung Ho: Seoul National University College of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Focal cortical dysplasia type I (FCD I) is the most common cause of pharmaco-resistant epilepsy with the poorest prognosis. To understand the epileptogenic mechanisms of FCD I, we obtained tissue resected from patients with FCD I epilepsy, and from tumor patients as control. Using whole-cell patch clamp in acute human brain slices, we investigated the cellular properties of fast-spiking interneurons (FSINs) and pyramidal neurons (PNs) within the ictal onset zone. In FCD I epilepsy, FSINs exhibited lower firing rates from slower repolarization and action potential broadening, while PNs had increased firing. Importantly, excitatory synaptic drive of FSINs increased progressively with the scale of cortical activation as a general property across species, but this relationship was inverted towards net inhibition in FCD I epilepsy. Further comparison with intracranial electroencephalography (iEEG) from the same patients revealed that the spatial extent of pathological high-frequency oscillations (pHFO) was associated with synaptic events at FSINs.

Date: 2024
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DOI: 10.1038/s41467-024-51065-7

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