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1.
iScience ; 27(2): 108846, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38318351

RESUMO

Visual processing depends on sensitive and balanced synaptic neurotransmission. Extracellular matrix proteins in the environment of cells are key modulators in synaptogenesis and synaptic plasticity. In the present study, we provide evidence that the combined loss of the four extracellular matrix components, brevican, neurocan, tenascin-C, and tenascin-R, in quadruple knockout mice leads to severe retinal dysfunction and diminished visual motion processing in vivo. Remarkably, impaired visual motion processing was accompanied by a developmental loss of cholinergic direction-selective starburst amacrine cells. Additionally, we noted imbalance of inhibitory and excitatory synaptic signaling in the quadruple knockout retina. Collectively, the study offers insights into the functional importance of four key extracellular matrix proteins for retinal function, visual motion processing, and synaptic signaling.

2.
Front Mol Neurosci ; 16: 1102334, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37143468

RESUMO

In the mammalian cortex a proper excitatory/inhibitory (E/I) balance is fundamental for cognitive functions. Especially γ-aminobutyric acid (GABA)-releasing interneurons regulate the activity of excitatory projection neurons which form the second main class of neurons in the cortex. During development, the maturation of fast-spiking parvalbumin-expressing interneurons goes along with the formation of net-like structures covering their soma and proximal dendrites. These so-called perineuronal nets (PNNs) represent a specialized form of the extracellular matrix (ECM, also designated as matrisome) that stabilize structural synapses but prevent the formation of new connections. Consequently, PNNs are highly involved in the regulation of the synaptic balance. Previous studies revealed that the formation of perineuronal nets is accompanied by an establishment of mature neuronal circuits and by a closure of critical windows of synaptic plasticity. Furthermore, it has been shown that PNNs differentially impinge the integrity of excitatory and inhibitory synapses. In various neurological and neuropsychiatric disorders alterations of PNNs were described and aroused more attention in the last years. The following review gives an update about the role of PNNs for the maturation of parvalbumin-expressing interneurons and summarizes recent findings about the impact of PNNs in different neurological and neuropsychiatric disorders like schizophrenia or epilepsy. A targeted manipulation of PNNs might provide an interesting new possibility to indirectly modulate the synaptic balance and the E/I ratio in pathological conditions.

3.
Front Cell Dev Biol ; 10: 886527, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35721494

RESUMO

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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