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GABAergic synapses onto SST and PV interneurons in the CA1 hippocampal region show cell-specific and integrin-dependent plasticity

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Brzdąk, Patrycja, Lebida, Katarzyna, Wyroślak, Marcin, Mozrzymas, Jerzy W.·2023·Scientific Reports
DOI 10.1038/s41598-023-31882-4PMC PMC10050003
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Abstract

It is known that GABAergic transmission onto pyramidal neurons shows different forms of plasticity. However, GABAergic cells innervate also other inhibitory interneurons and plasticity phenomena at these projections remain largely unknown. Several mechanisms underlying plastic changes, both at inhibitory and excitatory synapses, show dependence on integrins, key proteins mediating interaction between intra- and extracellular environment. We thus used hippocampal slices to address the impact of integrins on long-term plasticity of GABAergic synapses on specific inhibitory interneurons (containing parvalbumin, PV + or somatostatin, SST +) known to innervate distinct parts of principal cells. Administration of RGD sequence-containing peptide induced inhibitory long-term potentiation (iLTP) at fast-spiking (FS) PV + as well as on SST + interneurons. Interestingly, treatment with a more specific peptide GA(C)RRETAWA(C)GA (RRETAWA), affecting α5β1 integrins, resulted in iLTP in SST + and iLTD in FS PV + interneurons. Brief exposure to NMDA is known to induce iLTP at GABAergic synapses on pyramidal cells. Intriguingly, application of this protocol for considered interneurons evoked iLTP in SST + and iLTD in PV + interneurons. Moreover, we showed that in SST + cells, NMDA-evoked iLTP depends on the incorporation of GABA A receptors containing α5 subunit to the synapses, and this iLTP is occluded by RRETAWA peptide, indicating a key role of α5β1 integrins. Altogether, our results revealed that plasticity of inhibitory synapses at GABAergic cells shows interneuron-specificity and show differences in the underlying integrin-dependent mechanisms. This is the first evidence that neuronal disinhibition may be a highly plastic process depending on interneuron type and integrins’ activity.

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  • NDR2 is a critical component in sustaining LTP via supporting β1 integrin-mediated signaling.

    “Together, these data align well with the role of integrin signaling in sustaining synaptic plasticity at the SC‐CA1 synapse (Brzdąk et al. 2023) and suggest that NDR2 is a critical component in sustaining LTP via supporting β1 integrin‐mediated signaling.”

    From The Serine/Threonine Kinase <scp>NDR2</scp> Regulates Integrin Signaling, Synapse Formation, and Synaptic Plasticity in the Hippocampus (2025) · cites this paper as Brzdąk et al. 2023

    The Results section (“α5β1 integrins are involved in NMDAR-dependent iLTP in SST + INs”; page unavailable) reports that interfering with α5β1 integrins abolished inhibitory long-term potentiation in CA1 interneurons. The Discussion (“Cell-specificity of GABAergic plasticity is associated with integrin-dependent mechanisms”; page unavailable) also reports prior evidence linking integrins to excitatory LTP, but this paper does not establish the cited role specifically at the SC–CA1 synapse. The sentence presents NDR2’s role as the citing authors’ own inference, not as a finding attributed to Brzdąk et al. (LLM, conf=0.84)

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  • These data align with the role of integrin signaling in sustaining synaptic plasticity at the SC-CA1 synapse.

    “Together, these data align well with the role of integrin signaling in sustaining synaptic plasticity at the SC‐CA1 synapse (Brzdąk et al. 2023) and suggest that NDR2 is a critical component in sustaining LTP via supporting β1 integrin‐mediated signaling.”

    From The Serine/Threonine Kinase <scp>NDR2</scp> Regulates Integrin Signaling, Synapse Formation, and Synaptic Plasticity in the Hippocampus (2025) · cites this paper as Brzdąk et al. 2023

    The Discussion (page not available) reports that interfering with integrins abolished LTP of excitatory transmission and that β1-integrin loss weakened NMDAR-dependent LTP. The paper’s own results concern inhibitory synapses onto CA1 interneurons; the cited passage does not establish that integrin signaling sustains plasticity specifically at the SC–CA1 synapse. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Brzdąk, P., Lebida, K., Wyroślak, M., & Mozrzymas, J. W.
Affiliations
Wroclaw Medical University (PL)
Corresponding author
  • Brzdąk, Patrycja
  • Lebida, Katarzyna
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2023-03-28
Volume
13
Issue
1
Pages
5079-5079
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-023-31882-4
PMC
PMC10050003
OpenAlex
W4361209210
Cited by
14
References
4
Citations by year
2026: 4 · 2025: 6 · 2024: 3 · 2023: 1
FWCI
1.70
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Narodowe Centrum Nauki (2018/31/B/NZ4/01998)
  • Ministerstwo Edukacji i Nauki (SMN/16/1284/2020)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Keywords
GABAergic synapses, integrins, alpha5beta1 integrin, somatostatin interneurons, parvalbumin interneurons, fast-spiking interneurons, RGD peptide, hippocampal CA1
MeSH terms
Hippocampus, Interneurons, Neuronal Plasticity, Parvalbumins, Receptors, GABA-A, Somatostatin, Synapses, Integrins, N-Methylaspartate, Pyramidal Cells, CA1 Region, Hippocampal

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