Plasticity in Single Axon Glutamatergic Connection to GABAergic Interneurons Regulates Complex Events in the Human Neocortex
Open accessAbstract
In the human neocortex, single excitatory pyramidal cells can elicit very large glutamatergic EPSPs (VLEs) in inhibitory GABAergic interneurons capable of triggering their firing with short (3-5 ms) delay. Similar strong excitatory connections between two individual neurons have not been found in nonhuman cortices, suggesting that these synapses are specific to human interneurons. The VLEs are crucial for generating neocortical complex events, observed as single pyramidal cell spike-evoked discharge of cell assemblies in the frontal and temporal cortices. However, long-term plasticity of the VLE connections and how the plasticity modulates neocortical complex events has not been studied. Using triple and dual whole-cell recordings from synaptically connected human neocortical layers 2-3 neurons, we show that VLEs in fast-spiking GABAergic interneurons exhibit robust activity-induced long-term depression (LTD). The LTD by single pyramidal cell 40 Hz spike bursts is specific to connections with VLEs, requires group I metabotropic glutamate receptors, and has a presynaptic mechanism. The LTD of VLE connections alters suprathreshold activation of interneurons in the complex events suppressing the discharge of fast-spiking GABAergic cells. The VLEs triggering the complex events may contribute to cognitive processes in the human neocortex, and their long-term plasticity can alter the discharging cortical cell assemblies by learning.
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There is evidence for significant neuronal differences between rodents and humans, including distinct membrane and synaptic properties and dendritic complexity of human neurons that might contribute to human-specific signal processing.
“Indeed there is evidence for significant neuronal differences between rodents and human; for example, distinct membrane8,9 and synaptic10–14 properties and dendritic complexity15–17 of human neurons might contribute to human specific signal processing.”
From Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type (2018) · cites this paper as [14]
Very large unitary EPSPs that drive human basket and axo-axonic cells to suprathreshold postsynaptic responses were not encountered on rosehip cells.
“Very large unitary EPSPs, described to drive human basket and axo-axonic cells to suprathreshold postsynaptic responses10,11,14, were not encountered on RCs.”
From Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type (2018) · cites this paper as [14]
The sample sizes used in this study are comparable to those in earlier publications.
“our sample sizes are similar to those reported in previous publications10,11,14.”
From Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type (2018) · cites this paper as [14]
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- Authors
- Szegedi, V., Paizs, M., Csakvari, E., Molnar, G., Barzo, P., Tamas, G., & Lamsa, K.
- Affiliations
- University of Szeged (HU)
- Corresponding author
- Lamsa, Karri
- Venue
- PLOS Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2016-11-09
- Volume
- 14
- Issue
- 11
- Pages
- e2000237
- ISSN
- 1544-9173 (ISSN-L)
- 1545-7885
- PMC
- PMC5102409
- OpenAlex
- W2551177094
- Cited by
- 75
- References
- 63
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 11 · 2023: 10 · 2022: 7 · 2021: 4 · 2020: 9 · 2019: 7 · 2018: 5 · 2017: 3
- FWCI
- 2.80
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- SZTE Publicatio Repozitórium (University of Szeged) (acceptedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- Magyar Tudományos Akadémia
- Nemzeti Kutatási és Technológiai Hivatal (VKSZ-14-1-2015-0155)
- Nemzeti Kutatási Fejlesztési és Innovációs Hivatal (GINOP-2, VKSZ_14-1-2015-0155, GINOP-2.3.2, GINOP-2.3.2-15-2016-00018, GINOP-2.3.2-15)
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- long-term depression, pyramidal neurons, glutamatergic synapses, human neocortex, complex events, group I metabotropic glutamate receptors, presynaptic plasticity, synaptic plasticity, layer 2/3 neurons
- MeSH terms
- Axons, gamma-Aminobutyric Acid, Humans, Interneurons, Neuronal Plasticity, Glutamic Acid, Neocortex, Long-Term Synaptic Depression
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