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Numbers of Granule Cells and GABAergic Boutons Are Correlated in Shrunken Sclerotic Hippocampi of Sea Lions with Temporal Lobe Epilepsy.

Overview

Authors: Megan Wyeth1, David D. R. Krucik1, Chloé J. Thorbrogger1, Cara Field2, Paul S. Buckmaster1,3
  1. Department of Comparative Medicine, Stanford University, Palo Alto, California 94304
  2. The Marine Mammal Center, Sausalito, California 94965
  3. Department of Neurology & Neurological Sciences, Stanford University, Palo Alto, California 94304
Institutions: Stanford University (United States); Marine Mammal Center (United States)
Journal: eNeuro, volume 13, issue 3, pages ENEURO.0389-25.2026
Dates: received 21 October 2025; accepted 2 March 2026; published online 24 March 2026; in print March 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1523/eneuro.0389-25.2026 · PMID 41802862 · PMCID PMC13027691 · OpenAlex W7134236989
Open access: gold, a free copy (OpenAlex)
Categories: histology / microscopy (modality), human (organism), epilepsy (population), cellular / molecular (subfield)
Methods: Statistics, Connectivity
Keywords: dentate gyrus, GABAergic, granule cell, interneuron, stereology, terminal
MeSH: Epilepsy, Temporal Lobe*, GABAergic Neurons*, Hippocampal Sclerosis*, Hippocampus*, Neurons*, Presynaptic Terminals*, Animals, Cell Count, Female, Glutamate Decarboxylase, Interneurons, Male, Sea Lions, Vesicular Inhibitory Amino Acid Transport Proteins (* major topic)
Journal subjects: Research Article: New Research, Disorders of the Nervous System
Topic: Neuroscience and Neuropharmacology Research (Cellular and Molecular Neuroscience, Neuroscience), according to OpenAlex
Funding: National Science Foundation (OCE-131821); HHS | NIH | National Institute of Environmental Health Sciences (DEHS) (ES021960); HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS) (NS107290, NS136433); HHS | NIH | NIH Office of the Director (OD) (OD010989, OD011121)
Citations: cited by 1 paper (Europe PMC); 87 references in the paper
Research resources: RRID:AB_2278725, RRID:AB_2336132, Polyclonal anti-VGAT RRID:AB_2571624, Monoclonal anti-GAD65/67 RRID:AB_2756510, RRID:AB_2827937

Abstract

A possible mechanism of temporal lobe epilepsy is insufficient inhibition of hippocampal dentate granule cells. Precipitating injuries that kill interneurons in the dentate gyrus might result in fewer inhibitory synapses with granule cells. To test this hypothesis, previous studies evaluated numbers or densities of interneurons, γ-amino butyric acid (GABA)ergic boutons, and inhibitory synapses in tissue from human patients with temporal lobe epilepsy and rodent models. However, those studies have limitations. Some of those limitations can be addressed by a large animal model. Sea lions (Zalophus californianus) can develop temporal lobe epilepsy naturally. Like humans, epileptic sea lions exhibit bilateral or unilateral hippocampal sclerosis (neuron loss) with granule cell vulnerability, but sea lions permit optimal tissue preservation and sampling, and good control subjects. To label interneuron cell bodies and GABAergic synaptic boutons, sea lion hippocampal tissue from both sexes was processed with immunohistochemistry for glutamic acid decarboxylase (GAD) and vesicular GABA transporter. Stereological techniques were used to evaluate the dentate gyrus of the entire hippocampus. Numbers of granule cells, GAD cells, and GABAergic boutons were substantially reduced in shrunken, sclerotic hippocampi. However, numbers of GABAergic boutons and granule cells were correlated. These findings indicate that, despite losses, numbers of GABAergic boutons scale with numbers of surviving granule cells.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 5 authors, 6 keywords, 14 MeSH terms, 4 funders, 85 references, 5 RRIDs.

Cite

This paper

Wyeth, M., Krucik, D. D. R., Thorbrogger, C. J., Field, C., & Buckmaster, P. S. (2026). Numbers of Granule Cells and GABAergic Boutons Are Correlated in Shrunken Sclerotic Hippocampi of Sea Lions with Temporal Lobe Epilepsy. eNeuro, 13(3), ENEURO.0389-25.2026. https://doi.org/10.1523/eneuro.0389-25.2026

BibTeX

@article{wyeth2026numbers,
author = {Wyeth, Megan and Krucik, David D. R. and Thorbrogger, Chloé J. and Field, Cara and Buckmaster, Paul S.},
title = {{Numbers of Granule Cells and GABAergic Boutons Are Correlated in Shrunken Sclerotic Hippocampi of Sea Lions with Temporal Lobe Epilepsy}},
journal = {eNeuro},
year = {2026},
month = mar,
volume = {13},
number = {3},
pages = {ENEURO.0389--25.2026},
publisher = {Society for Neuroscience},
issn = {2373-2822},
doi = {10.1523/eneuro.0389-25.2026},
url = {https://doi.org/10.1523/eneuro.0389-25.2026},
pmid = {41802862},
pmcid = {PMC13027691}
}

RIS

TY - JOUR
AU - Wyeth, Megan
AU - Krucik, David D. R.
AU - Thorbrogger, Chloé J.
AU - Field, Cara
AU - Buckmaster, Paul S.
TI - Numbers of Granule Cells and GABAergic Boutons Are Correlated in Shrunken Sclerotic Hippocampi of Sea Lions with Temporal Lobe Epilepsy
T2 - eNeuro
J2 - eNeuro
PY - 2026
DA - 2026/03/25
VL - 13
IS - 3
SP - ENEURO.0389
EP - 25.2026
SN - 2373-2822
PB - Society for Neuroscience
DO - 10.1523/eneuro.0389-25.2026
UR - https://doi.org/10.1523/eneuro.0389-25.2026
LA - en
ER -

CSL-JSON

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