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Updated: Jul 15, 2025
Investigating Long-term Synaptic Plasticity in Interlamellar Hippocampus CA1 by Electrophysiological Field Recording
Published on: August 11, 2019
Evolutionary conservation of hippocampal mossy fiber synapse properties
Kenneth A Pelkey1, Geoffrey A Vargish1, Leonardo V Pellegrini2
1Eunice Kennedy Shriver National Institute of Child Health and Human Development Intramural Research Program, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract:
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.
Insights
Human hippocampal mossy fiber (MF) synapses share core functional properties with rodents, crucial for memory. Deficits in inhibitory tone onto these MF synapses may drive epilepsy.
Area of Science:
- Neuroscience
- Synaptic Plasticity
- Epilepsy Research
Background:
- Hippocampal mossy fiber (MF) synapses are vital for memory encoding.
- Previous research primarily focused on rodent models, with limited human data.
- Understanding human MF function is crucial for translational relevance.
Purpose of the Study:
- To investigate the functional properties of human MF synapses.
- To compare human MF properties with those established in rodent models.
- To explore the role of MF synapses in human epilepsy.
Main Methods:
- Electrophysiological evaluation of MF synapses in human epilepsy-resected tissue.
- Array tomography for ultrastructural analysis.
- Comparison of human data with established rodent MF synapse characteristics.
Main Results:
- Human MFs exhibit conserved properties: AMPA receptor dominance, NMDA/kainate receptor minor roles, large dynamic range, frequency facilitation, NMDA-independent LTP, and cAMP-sensitive release.
- Ultrastructure is evolutionarily conserved, confirmed by array tomography.
- Human MFs show reduced GABAergic inhibitory tone, suggesting excessive excitatory drive in epilepsy.
Conclusions:
- Core functional properties of human MF synapses are highly conserved across species.
- Rodent models accurately reflect fundamental human MF synapse physiology.
- Impaired inhibition on human MF synapses may contribute to epileptic hyperexcitability.
