Extracellular matrix integrity regulates GABAergic plasticity in the hippocampus.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Netherlands NLM ID: 9432592 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1569-1802 (Electronic) Linking ISSN: 0945053X NLM ISO Abbreviation: Matrix Biol Subsets: MEDLINE
    • Publication Information:
      Publication: Amsterdam : Elsevier
      Original Publication: Stuttgart ; New York : Fischer, c1994-
    • Subject Terms:
      Extracellular Matrix*/metabolism ; Neuronal Plasticity* ; Pyramidal Cells*/metabolism ; Hyaluronoglucosaminidase*/metabolism ; Hyaluronoglucosaminidase*/genetics; Animals ; Mice ; Hyaluronic Acid/metabolism ; Chondroitin Sulfate Proteoglycans/metabolism ; Chondroitin Sulfate Proteoglycans/genetics ; Synaptic Transmission ; Chondroitin ABC Lyase/metabolism ; Chondroitin ABC Lyase/pharmacology ; GABAergic Neurons/metabolism ; Synapses/metabolism ; Interneurons/metabolism ; Inhibitory Postsynaptic Potentials ; Male ; Parvalbumins/metabolism ; Parvalbumins/genetics ; CA1 Region, Hippocampal/metabolism ; CA1 Region, Hippocampal/cytology ; Somatostatin/metabolism ; Somatostatin/genetics ; Hippocampus/metabolism ; Hippocampus/cytology
    • Abstract:
      The brain's extracellular matrix (ECM) is crucial for neural circuit functionality, synaptic plasticity, and learning. While the role of the ECM in excitatory synapses has been extensively studied, its influence on inhibitory synapses, particularly on GABAergic long-term plasticity, remains poorly understood. This study aims to elucidate the effects of ECM components on inhibitory synaptic transmission and plasticity in the hippocampal CA1 region. We focus on the roles of chondroitin sulfate proteoglycans (CSPGs) and hyaluronic acid in modulating inhibitory postsynaptic currents (IPSCs) at two distinct inhibitory synapses formed by somatostatin (SST)-positive and parvalbumin (PV)-positive interneurons onto pyramidal cells (PCs). Using optogenetic stimulation in brain slices, we observed that acute degradation of ECM constituents by hyaluronidase or chondroitinase-ABC did not affect basal inhibitory synaptic transmission. However, short-term plasticity, particularly burst-induced depression, was enhanced at PV→PC synapses following enzymatic treatments. Long-term plasticity experiments demonstrated that CSPGs are essential for NMDA-induced iLTP at SST→PC synapses, whereas the digestion of hyaluronic acid by hyaluronidase impaired iLTP at PV→PC synapses. This indicates a synapse-specific role of CSPGs and hyaluronic acid in regulating GABAergic plasticity. Additionally, we report the presence of cryptic GABAergic plasticity at PV→PC synapses induced by prolonged NMDA application, which became evident after CSPG digestion and was absent under control conditions. Our results underscore the differential impact of ECM degradation on inhibitory synaptic plasticity, highlighting the synapse-specific interplay between ECM components and specific GABAergic synapses. This offers new perspectives in studies on learning and critical period timing.
      Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose.
      (Copyright © 2024. Published by Elsevier B.V.)
    • Contributed Indexing:
      Keywords: Extracellular matrix; GABA; Hyaluronic acid; Inhibitory plasticity; Perineuronal nets; Proteoglycans; iLTP
    • Accession Number:
      EC 3.2.1.35 (Hyaluronoglucosaminidase)
      9004-61-9 (Hyaluronic Acid)
      0 (Chondroitin Sulfate Proteoglycans)
      EC 4.2.2.20 (Chondroitin ABC Lyase)
      0 (Parvalbumins)
      51110-01-1 (Somatostatin)
    • Publication Date:
      Date Created: 20241104 Date Completed: 20241123 Latest Revision: 20241123
    • Publication Date:
      20241126
    • Accession Number:
      10.1016/j.matbio.2024.11.001
    • Accession Number:
      39491759