---
title: "Presynaptic basis of epileptiform rhythms in forward-programmed human excitatory neuronal networks"
id: "biorxiv-14-presynaptic-mechanism-of-epileptiform-activities-in-forward-programmed-human"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-14-presynaptic-mechanism-of-epileptiform-activities-in-forward-programmed-human"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.08.04.742761v1?rss=1"
published_at: "2026-08-10T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Presynaptic basis of epileptiform rhythms in forward-programmed human excitatory neuronal networks
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-14-presynaptic-mechanism-of-epileptiform-activities-in-forward-programmed-human
- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.08.04.742761v1?rss=1)
- **Published At:** 2026-08-10T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study used **human iPSC-derived excitatory neurons** generated by targeted **forward-programming** to form cultured neuronal networks that reproduce epilepsy-like activity. - Networks produced glutamate-dependent, epileptiform **super-bursts** characterized by a progressive slowing of spike rhythm from about ~4 Hz to ~2 Hz before termination. - Authors combined **in silico** simulations and **in vitro** experiments to link the observed temporal patterning to presynaptic vesicle pool organization. - Nested burst structure was associated with the **recycling pool (RP)** of synaptic vesicles, while faster sub-bursts related to the **readily releasable pool (RRP)**. - Slowing of RP-to-RRP vesicle translocation shortened the duration of super-bursts, implicating vesicle translocation kinetics as a determinant of epileptiform dynamics. - The work positions forward-programmed human excitatory networks as a model system for investigating mechanisms of rhythmic discharges and seizure termination, emphasizing a **presynaptic** framework. - The article is a preprint; it has not been peer reviewed. Funder support includes the China Scholarship Council and the University of Bonn. Authors declared no competing interests.
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Jianbin Wen 1 Institute of Reconstructive Neurobiology, University of Bonn Medical Faculty & University Hospital Bonn, Germany; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Jianbin%2BWen%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Wen%20J&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AJianbin%2BWen%2B) Jiaqing Li 2 Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Jiaqing%2BLi%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Li%20J&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AJiaqing%2BLi%2B) Michael Peitz 1 Institute of Reconstructive Neurobiology, University of Bonn Medical Faculty & University Hospital Bonn, Germany; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Michael%2BPeitz%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Peitz%20M&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AMichael%2BPeitz%2B) Oliver Bruestle 1 Institute of Reconstructive Neurobiology, University of Bonn Medical Faculty & University Hospital Bonn, Germany; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Oliver%2BBruestle%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Bruestle%20O&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AOliver%2BBruestle%2B) * For correspondence: brustle@uni-bonn.de * [Abstract](https://www.biorxiv.org/content/10.64898/2026.08.04.742761v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5694265/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.08.04.742761v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5694265/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.08.04.742761v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5694265/1) * [Supplementary material](https://www.biorxiv.org/content/10.64898/2026.08.04.742761v1.supplementary-material)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_data/node:5694265/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.08.04.742761v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5694265/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## Abstract Epilepsy is one of the most common neurological disorders, yet the mechanisms controlling seizure termination remain poorly understood. In particular, why rhythmic spike-wave discharges decelerate before stopping is unexplained. Here, using human iPSC-derived excitatory neurons differentiated via targeted forward-programming, we report a similar deceleration phenomenon in cultured neuronal networks. These networks exhibit glutamate-dependent, epileptiform 'super-bursts' with a slowing rhythm from ~4 Hz to ~2 Hz. Combining in silico simulations and in vitro experiments, we correlate this activity pattern with the hierarchical organization of presynaptic vesicle pools. Nested bursts link to the recycling pool (RP), and sub-bursts associate with the readily releasable pool (RRP). Decelerating RP-to-RRP vesicle translocation shortened the super-bursts, indicating that epileptiform dynamics depend heavily on this translocation process. These findings depict human neuronal networks derived from forward-programmed cells as a model for epileptology, revealing a presynaptic framework for rhythmic discharges in excitatory networks. ### Competing Interest Statement The authors have declared no competing interest. ## Funder Information Declared China Scholarship Council, https://ror.org/04atp4p48 University of Bonn, https://ror.org/041nas322 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. bioRxiv and medRxiv thank the following for their generous financial support: > The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, The University of Edinburgh, University of Washington, and Vrije Universiteit Amsterdam. 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[ Download PDF](https://www.biorxiv.org/content/10.64898/2026.08.04.742761v1.full.pdf) Print/Save Options [Download PDF](https://www.biorxiv.org/content/biorxiv/early/2026/08/10/2026.08.04.742761.full.pdf)Full Text & In-line FiguresXML [More Info](https://www.biorxiv.org/about/FAQ#PrintOptions "More Information on Print/Save Options") [Supplementary Material ](https://www.biorxiv.org/content/10.64898/2026.08.04.742761v1.supplementary-material) [ Email](https://www.biorxiv.org/ "Email this Article") [ Share](https://www.biorxiv.org/) Presynaptic mechanism of epileptiform activities in forward-programmed human excitatory neuronal networks Jianbin Wen, Jiaqing Li, Michael Peitz, Oliver Bruestle bioRxiv 2026.08.04.742761; doi: https://doi.org/10.64898/2026.08.04.742761 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. 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