Microscale maps of bursting dynamics across human hippocampal slices from patients with epilepsy
Neuronal firing patterning in the dentate gyrus of patients with epilepsy remains unknown at the microcircuit level. Advancements in high-density CMOS-based microelectrode arrays can be harnessed to study network activity with unprecedented spatial and temporal resolution. We use novel computational methods with high-density electrophysiology recordings to spatially map network activity of human hippocampal brain slices from six patients with mesial temporal lobe epilepsy. Two slices from the dentate gyrus exhibited synchronous bursting activity in the presence of low magnesium media with kainic acid, representative of seizure-like behavior. We bridged microscale circuit dynamics with alterations in theta oscillations at the network scale. Future studies may apply this approach to spatially elucidate functional networks and their possible role in seizures.<b>NEW & NOTEWORTHY</b> We apply high-density CMOS-based microelectrode arrays to excised patient brain slices, mapping the communication patterns of hundreds of neurons at unprecedented resolution. We developed novel computational techniques to spatially map neuronal dynamics. In patient slices, our findings suggest that recurrent feedback localized within the dentate gyrus of the hippocampus is linked to a previously unreported phenomenon of theta propagations. This bridges microscale circuit dynamics with alterations in theta oscillations.
Authors
- Kateryna Voitiuk (ORCID: https://orcid.org/0000-0002-6392-5188)
- Tjitse van der Molen (ORCID: https://orcid.org/0000-0001-6147-542X)
- David F. Parks (ORCID: https://orcid.org/0000-0002-4635-8206)
- Mircea Teodorescu (ORCID: https://orcid.org/0000-0001-7085-5248)
- John P. Andrews (ORCID: https://orcid.org/0000-0002-8025-1525)
- Jinghui Geng (ORCID: https://orcid.org/0000-0002-3431-9568)
- Ash Robbins (ORCID: https://orcid.org/0000-0002-5556-8547)
- Matthew A.T. Elliott (ORCID: https://orcid.org/0000-0001-6313-6819)
- Alex Spaeth (ORCID: https://orcid.org/0000-0003-0702-3945)
- Tal Sharf (ORCID: https://orcid.org/0000-0002-7899-2818)
- David García Solís (ORCID: https://orcid.org/0009-0002-3261-7833)
- David H. Haussler (ORCID: https://orcid.org/0000-0003-1533-4575)
- Edward F. Chang (ORCID: https://orcid.org/0000-0003-2480-4700)
- Cordero Core (ORCID: https://orcid.org/0000-0002-3531-3221)
- Álvaro Toledo
- Tom Gillespie
- Ari Sinervo
Institutions
- Software Engineering Institute (US)
- University of California, Santa Barbara (US)
- University of California, San Francisco (US)
- University of California, Santa Cruz (US)
- University of Washington (US)
- Broad Center (US)
- Neurological Surgery (US)
Publication Details
- Journal
- Journal of Neurophysiology
- Published
- 2025-12-12
- DOI
- https://doi.org/10.1152/jn.00217.2025
- Primary Topic
- Neural dynamics and brain function
- Type
- article
- Field-Weighted Citation Impact
- 0.00