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Lookup NU author(s): Dr Mark EldridgeORCiD
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© 2023. 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.
Author(s): Pelkey KA, Vargish GA, Pellegrini LV, Calvigioni D, Chapeton J, Yuan X, Hunt S, Cummins AC, Eldridge MAG, Pickel J, Chittajallu R, Averbeck BB, Toth K, Zaghloul K, McBain CJ
Publication type: Article
Publication status: Published
Journal: Neuron
Year: 2023
Volume: 111
Issue: 23
Pages: 3802-3818.e5
Print publication date: 06/12/2023
Online publication date: 29/09/2023
Acceptance date: 06/09/2023
ISSN (print): 0896-6273
ISSN (electronic): 1097-4199
Publisher: Cell Press
URL: https://doi.org/10.1016/j.neuron.2023.09.005
DOI: 10.1016/j.neuron.2023.09.005
PubMed id: 37776852
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