The fasciola cinereum of the hippocampal tail as an interventional target in epilepsy

Ryan M Jamiolkowski; Quynh-Anh Nguyen; Jordan S Farrell; Ryan J McGinn; David A Hartmann; Jeff J Nirschl; Mateo I Sanchez; Vivek P Buch; Ivan Soltesz

doi:10.1038/s41591-024-02924-9

The fasciola cinereum of the hippocampal tail as an interventional target in epilepsy

Nat Med. 2024 Apr 17. doi: 10.1038/s41591-024-02924-9. Online ahead of print.

Authors

Ryan M Jamiolkowski^#¹, Quynh-Anh Nguyen^#^{2

3}, Jordan S Farrell^{4

5}, Ryan J McGinn⁶, David A Hartmann⁶, Jeff J Nirschl⁷, Mateo I Sanchez⁸, Vivek P Buch⁴, Ivan Soltesz⁴

Affiliations

¹ Department of Neurosurgery, Stanford University, Stanford, CA, USA. ryanjam@stanford.edu.
² Department of Neurosurgery, Stanford University, Stanford, CA, USA. qa.nguyen@vanderbilt.edu.
³ Department of Pharmacology and the Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA. qa.nguyen@vanderbilt.edu.
⁴ Department of Neurosurgery, Stanford University, Stanford, CA, USA.
⁵ F.M. Kirby Neurobiology Center and Rosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
⁶ Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
⁷ Department of Pathology, Stanford University, Stanford, CA, USA.
⁸ Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK.

^# Contributed equally.

PMID: 38632391
DOI: 10.1038/s41591-024-02924-9

Abstract

Targeted tissue ablation involving the anterior hippocampus is the standard of care for patients with drug-resistant mesial temporal lobe epilepsy. However, a substantial proportion continues to suffer from seizures even after surgery. We identified the fasciola cinereum (FC) neurons of the posterior hippocampal tail as an important seizure node in both mice and humans with epilepsy. Genetically defined FC neurons were highly active during spontaneous seizures in epileptic mice, and closed-loop optogenetic inhibition of these neurons potently reduced seizure duration. Furthermore, we specifically targeted and found the prominent involvement of FC during seizures in a cohort of six patients with epilepsy. In particular, targeted lesioning of the FC in a patient reduced the seizure burden present after ablation of anterior mesial temporal structures. Thus, the FC may be a promising interventional target in epilepsy.

Abstract

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