Brevican, Neurocan, Tenascin-C and Tenascin-R Act as Important Regulators of the Interplay between Perineuronal Nets, Synaptic Integrity, Inhibitory Interneurons and Otx2

Mueller-Buehl, Cornelius; Reinhard, Jacqueline; Roll, Lars; Bader, Verian; Winklhofer, Konstanze F.; Faissner, Andréas

doi:10.1101/2022.02.24.481837

Cited by 2 publications

(2 citation statements)

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“…For instance, tenascin R interacts with GABAB receptors, modulating presynaptic activity to increase basal excitatory transmission while reducing perisomatic GABAergic inhibition [7]. Additionally, mice concurrently deficient in brevican, neurocan, tenascin-C, and -R exhibit a synaptic excitatory/inhibitory imbalance, with increased decreased number of inhibitory synapses within the PNNs [8]. Acute modifications of the brain ECM also impact inhibitory function.…”

Section: Introductionmentioning

confidence: 99%

Extracellular matrix integrity regulates GABAergic plasticity in the hippocampus

Jabłońska,

Wiera,

Mozrzymas

2024

Preprint

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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.

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Section: Introductionmentioning

confidence: 99%

Extracellular matrix integrity regulates GABAergic plasticity in the hippocampus

Jabłońska,

Wiera,

Mozrzymas

2024

Preprint

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“…This manuscript has been released as a pre-print at bioRxiv ( Mueller-Buehl et al, 2022 ). The authors thank Anja Coenen, Sabine Kindermann, and Franziska Mennes for technical assistance.…”

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confidence: 99%

Brevican, Neurocan, Tenascin-C, and Tenascin-R Act as Important Regulators of the Interplay Between Perineuronal Nets, Synaptic Integrity, Inhibitory Interneurons, and Otx2

Mueller-Buehl

Reinhard

Roll

et al. 2022

Front. Cell Dev. Biol.

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Fast-spiking parvalbumin interneurons are critical for the function of mature cortical inhibitory circuits. Most of these neurons are enwrapped by a specialized extracellular matrix (ECM) structure called perineuronal net (PNN), which can regulate their synaptic input. In this study, we investigated the relationship between PNNs, parvalbumin interneurons, and synaptic distribution on these cells in the adult primary visual cortex (V1) of quadruple knockout mice deficient for the ECM molecules brevican, neurocan, tenascin-C, and tenascin-R. We used super-resolution structured illumination microscopy (SIM) to analyze PNN structure and associated synapses. In addition, we examined parvalbumin and calretinin interneuron populations. We observed a reduction in the number of PNN-enwrapped cells and clear disorganization of the PNN structure in the quadruple knockout V1. This was accompanied by an imbalance of inhibitory and excitatory synapses with a reduction of inhibitory and an increase of excitatory synaptic elements along the PNNs. Furthermore, the number of parvalbumin interneurons was reduced in the quadruple knockout, while calretinin interneurons, which do not wear PNNs, did not display differences in number. Interestingly, we found the transcription factor Otx2 homeoprotein positive cell population also reduced. Otx2 is crucial for parvalbumin interneuron and PNN maturation, and a positive feedback loop between these parameters has been described. Collectively, these data indicate an important role of brevican, neurocan, tenascin-C, and tenascin-R in regulating the interplay between PNNs, inhibitory interneurons, synaptic distribution, and Otx2 in the V1.

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Brevican, Neurocan, Tenascin-C and Tenascin-R Act as Important Regulators of the Interplay between Perineuronal Nets, Synaptic Integrity, Inhibitory Interneurons and Otx2

Cited by 2 publications

References 81 publications

Extracellular matrix integrity regulates GABAergic plasticity in the hippocampus

Extracellular matrix integrity regulates GABAergic plasticity in the hippocampus

Brevican, Neurocan, Tenascin-C, and Tenascin-R Act as Important Regulators of the Interplay Between Perineuronal Nets, Synaptic Integrity, Inhibitory Interneurons, and Otx2

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