Dataset Information

Elimination of the four extracellular matrix molecules tenascin-C, tenascin-R, brevican and neurocan alters the ratio of excitatory and inhibitory synapses.

ABSTRACT: The synaptic transmission in the mammalian brain is not limited to the interplay between the pre- and the postsynapse of neurons, but involves also astrocytes as well as extracellular matrix (ECM) molecules. Glycoproteins, proteoglycans and hyaluronic acid of the ECM pervade the pericellular environment and condense to special superstructures termed perineuronal nets (PNN) that surround a subpopulation of CNS neurons. The present study focuses on the analysis of PNNs in a quadruple knockout mouse deficient for the ECM molecules tenascin-C (TnC), tenascin-R (TnR), neurocan and brevican. Here, we analysed the proportion of excitatory and inhibitory synapses and performed electrophysiological recordings of the spontaneous neuronal network activity of hippocampal neurons in vitro. While we found an increase in the number of excitatory synaptic molecules in the quadruple knockout cultures, the number of inhibitory synaptic molecules was significantly reduced. This observation was complemented with an enhancement of the neuronal network activity level. The in vivo analysis of PNNs in the hippocampus of the quadruple knockout mouse revealed a reduction of PNN size and complexity in the CA2 region. In addition, a microarray analysis of the postnatal day (P) 21 hippocampus was performed unravelling an altered gene expression in the quadruple knockout hippocampus.

SUBMITTER: Gottschling C

PROVIDER: S-EPMC6763627 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Elimination of the four extracellular matrix molecules tenascin-C, tenascin-R, brevican and neurocan alters the ratio of excitatory and inhibitory synapses.

Gottschling Christine C Wegrzyn David D Denecke Bernd B Faissner Andreas A

Scientific reports 20190926 1

The synaptic transmission in the mammalian brain is not limited to the interplay between the pre- and the postsynapse of neurons, but involves also astrocytes as well as extracellular matrix (ECM) molecules. Glycoproteins, proteoglycans and hyaluronic acid of the ECM pervade the pericellular environment and condense to special superstructures termed perineuronal nets (PNN) that surround a subpopulation of CNS neurons. The present study focuses on the analysis of PNNs in a quadruple knockout mous ...[more]

PMID: 31558805

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Project description:A key feature of excitatory synapses is the existence of subsynaptic protein nanoclusters whose precise alignment across the cleft in a trans-synaptic nanocolumn influences the strength of synaptic transmission. However, whether nanocolumn properties vary between excitatory synapses functioning in different cellular contexts is unknown. We used a combination of confocal and DNA-PAINT super-resolution microscopy to directly compare the organization of shared scaffold proteins at two important excitatory synapses - those forming onto excitatory principal neurons (Ex→Ex synapses) and those forming onto parvalbumin-expressing interneurons (Ex→PV synapses). As in Ex→Ex synapses, we find that in Ex→PV synapses presynaptic Munc13-1 and postsynaptic PSD-95 both form nanoclusters that demonstrate alignment, underscoring synaptic nanostructure and the trans-synaptic nanocolumn as conserved organizational principles of excitatory synapses. Despite the general conservation of these features, we observed specific differences in the characteristics of pre- and postsynaptic Ex→PV nanostructure. Ex→PV synapses contained larger PSDs with fewer PSD-95 NCs when accounting for size than Ex→Ex synapses. Furthermore, the PSD-95 NCs were larger and denser. The identity of the postsynaptic cell also had a retrograde impact on Munc13-1 organization, as Ex→PV synapses hosted larger Munc13-1 puncta that contained less dense but larger and more numerous Munc13-1 NCs. Moreover, we measured the spatial variability of transsynaptic alignment in these synapse types, revealing protein alignment in Ex→PV synapses over a distinct range of distances compared to Ex→Ex synapses. We conclude that while general principles of nanostructure and alignment are shared, cell-specific elements of nanodomain organization likely contribute to functional diversity of excitatory synapses. Understanding the rules of synapse nanodomain assembly, which themselves are cell-type specific, will be essential for illuminating brain network dynamics.

Dataset Information

Elimination of the four extracellular matrix molecules tenascin-C, tenascin-R, brevican and neurocan alters the ratio of excitatory and inhibitory synapses.

Publications

Elimination of the four extracellular matrix molecules tenascin-C, tenascin-R, brevican and neurocan alters the ratio of excitatory and inhibitory synapses.

Similar Datasets

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