Geissler, Maren and Gottschling, Christine and Aguado, Ainhara and Rauch, Uwe and Wetzel, Christian H. and Hatt, Hanns and Faissner, Andreas (2013) Primary Hippocampal Neurons, Which Lack Four Crucial Extracellular Matrix Molecules, Display Abnormalities of Synaptic Structure and Function and Severe Deficits in Perineuronal Net Formation. JOURNAL OF NEUROSCIENCE, 33 (18). 7742-+. ISSN 0270-6474,
Full text not available from this repository. (Request a copy)Abstract
The extracellular matrix (ECM) of the brain plays crucial roles during the development, maturation, and regeneration of the CNS. In a subpopulation of neurons, the ECM condenses to superstructures called perineuronal nets (PNNs) that surround synapses. Camillo Golgi described PNNs a century ago, yet their biological functions remain elusive. Here, we studied a mouse mutant that lacks four ECM components highly enriched in the developing brain: the glycoproteins tenascin-C and tenascin-R and the chondroitin sulfate proteoglycans brevican and neurocan. Primary embryonic hippocampal neurons and astrocytes were cultivated using a cell insert system that allows for co-culture of distinct cell populations in the absence of direct membrane contacts. The wild-type and knock-out cells were combined in the four possible permutations. Using this approach, neurons cultivated in the presence of mutant astrocytes displayed a transient increase of synapses after 2 weeks. However, after a period of 3 weeks or longer, synapse formation and stabilization were compromised when either neuron or astrocyte cell populations or both were of mutant origin. The development of PNN structures was observed, but their size was substantially reduced on knock-out neurons. The synaptic activity of both wild-type and knock-out neurons was monitored using whole-cell patch clamping. The salient observation was a reduced frequency of IPSCs and EPSCs, whereas the amplitudes were not modified. Remarkably, the knock-out neuron phenotypes could not be rescued by wild-type astrocytes. We conclude that the elimination of four ECM genes compromises neuronal function.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHONDROITIN SULFATE PROTEOGLYCANS; CENTRAL-NERVOUS-SYSTEM; LONG-TERM POTENTIATION; GLYCOPROTEIN TENASCIN-R; SPINAL-CORD-INJURY; C MESSENGER-RNA; CNS SYNAPTOGENESIS; PERISOMATIC INHIBITION; POSTNATAL-DEVELOPMENT; CEREBRAL-CORTEX; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie > Molekulare Neurowissenscahften |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Apr 2020 13:04 |
| Last Modified: | 15 Apr 2020 13:04 |
| URI: | https://pred.uni-regensburg.de/id/eprint/16727 |
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