Evolutionary conservation of hippocampal mossy fiber synapse properties.

dentate epilepsy evolution hippocampus human mossy fiber

Journal

Neuron
ISSN: 1097-4199
Titre abrégé: Neuron
Pays: United States
ID NLM: 8809320

Informations de publication

Date de publication:
06 Dec 2023
Historique:
received: 07 02 2023
revised: 03 07 2023
accepted: 06 09 2023
pubmed: 1 10 2023
medline: 1 10 2023
entrez: 30 9 2023
Statut: ppublish

Résumé

Various specialized structural/functional properties are considered essential for contextual memory encoding by hippocampal mossy fiber (MF) synapses. Although investigated to exquisite detail in model organisms, synapses, including MFs, have undergone minimal functional interrogation in humans. To determine the translational relevance of rodent findings, we evaluated MF properties within human tissue resected to treat epilepsy. Human MFs exhibit remarkably similar hallmark features to rodents, including AMPA receptor-dominated synapses with small contributions from NMDA and kainate receptors, large dynamic range with strong frequency facilitation, NMDA receptor-independent presynaptic long-term potentiation, and strong cyclic AMP (cAMP) sensitivity of release. Array tomography confirmed the evolutionary conservation of MF ultrastructure. The astonishing congruence of rodent and human MF core features argues that the basic MF properties delineated in animal models remain critical to human MF function. Finally, a selective deficit in GABAergic inhibitory tone onto human MF postsynaptic targets suggests that unrestrained detonator excitatory drive contributes to epileptic circuit hyperexcitability.

Identifiants

DOI: 10.1016/j.neuron.2023.09.005 PMID: 37776852
pubmed: 37776852
pii: S0896-6273(23)00669-4
doi: 10.1016/j.neuron.2023.09.005
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

3802-3818.e5

Informations de copyright

Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Kenneth A Pelkey (KA)

Eunice Kennedy Shriver National Institute of Child Health and Human Development Intramural Research Program, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: pelkeyk2@mail.nih.gov.

Geoffrey A Vargish (GA)

Eunice Kennedy Shriver National Institute of Child Health and Human Development Intramural Research Program, National Institutes of Health, Bethesda, MD 20892, USA.

Leonardo V Pellegrini (LV)

Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Brain and Mind Research Institute, Ottawa, ON K1H 8M5, Canada.

Daniela Calvigioni (D)

Eunice Kennedy Shriver National Institute of Child Health and Human Development Intramural Research Program, National Institutes of Health, Bethesda, MD 20892, USA.

Julio Chapeton (J)

National Institute of Neurological Disorders and Stroke Intramural Research Program, National Institutes of Health, Bethesda, MD 20892, USA.

Xiaoqing Yuan (X)

Eunice Kennedy Shriver National Institute of Child Health and Human Development Intramural Research Program, National Institutes of Health, Bethesda, MD 20892, USA.

Steven Hunt (S)

Eunice Kennedy Shriver National Institute of Child Health and Human Development Intramural Research Program, National Institutes of Health, Bethesda, MD 20892, USA.

Alex C Cummins (AC)

National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.

Mark A G Eldridge (MAG)

National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.

James Pickel (J)

National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.

Ramesh Chittajallu (R)

Eunice Kennedy Shriver National Institute of Child Health and Human Development Intramural Research Program, National Institutes of Health, Bethesda, MD 20892, USA.

Bruno B Averbeck (BB)

National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.

Katalin Tóth (K)

Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Brain and Mind Research Institute, Ottawa, ON K1H 8M5, Canada.

Kareem Zaghloul (K)

National Institute of Neurological Disorders and Stroke Intramural Research Program, National Institutes of Health, Bethesda, MD 20892, USA.

Chris J McBain (CJ)

Eunice Kennedy Shriver National Institute of Child Health and Human Development Intramural Research Program, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: mcbainc@mail.nih.gov.

Classifications MeSH