Cellular environment controls formation and activity of neuronal connections

Neuron in the net: The illustration shows a neuron from the hippocampus of a mouse in cell culture, which is surrounded by a special structure of the extracellular matrix - a perineuronal net (blue). Various structures of the synapse are coloured red, green and yellow. © RUB, LS Zellmorphologie und Molekulare Neurobiologie (Department of Cell Morphology and Molecular Neurobiology)

Environment moulds behaviour - and not just that of people in society, but also at the microscopic level. This is because, for their function, neurons are dependent on the cell environment, the so-termed extracellular matrix. Researchers at the Ruhr-Universität have found evidence that this complex network of molecules controls the formation and activity of the neuronal connections. The team led by Dr. Maren Geißler und Prof. Andreas Faissner from the Department of Cell Morphology and Molecular Neurobiology reports in the Journal of Neuroscience in collaboration with the team of Dr. Ainhara Aguado, Prof. Christian Wetzel and Prof. Hanns Hatt from the Department of Cell Physiology.

In cooperation with Prof. Uwe Rauch from Lund University in Sweden, Bochum's biologists examined cells from the brains of two mouse species: a species with a normal extracellular matrix and a species which lacked four components of the extracellular matrix due to , namely the molecules tenascin-C, tenascin-R, neurocan and brevican. They took the cells from the hippocampus, a that is crucial for the long-term memory. The team not only examined neurons but also astrocytes, which are in close contact with the neurons, support their function and secrete molecules for the extracellular matrix.

Formation, stability and activity of the neuronal connections depend on the matrix

The researchers cultivated the neurons and astrocytes together for four weeks with a specially developed culture strategy. Among other things, they observed how many connections, known as synapses, the neurons formed with each other and how stable these were over time. If either the or the neurons in the culture dish derived from animals with a reduced extracellular matrix, these synapses proved to be less stable in the medium term, and their number was significantly reduced. Together with the Department of Cell Physiology at the RUB and the University of Regensburg, the team also showed that the neurons with a mutated matrix showed lower spontaneous activity than normal cells. The extracellular matrix thus regulates the formation, stability and activity of the . The researchers also examined a special structure of the extracellular matrix, the so-called perineuronal nets, which the Nobel laureate Camillo Golgi first described more than a century ago. They were significantly reduced in the environment of genetically modified cells.

More information: M. Geissler, C. Gottschling, A. Aguado, U. Rauch, C.H. Wetzel, H. Hatt, A. Faissner (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, DOI: 10.1523/JNEUROSCI.3275-12.2013

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JVK
1 / 5 (1) May 07, 2013
Excerpt: "We conclude that the elimination of four ECM genes compromises neuronal function." Conclusion: "Therefore, the quadruple mutant represents a valuable model system with which to study neuronal development in general and synaptic plasticity in particular."
I suspect people are confused by the terms used. The quadruple 'mutant' represents perturbation of nutrient-dependent pheromone-controlled adaptive evolution, which involves genes of large effect that are essential for meeting Darwin's 'conditions of life.' His conditions of life precede natural selection that must some enable conservation of genes of large effect. Those who posit that mutations are involved in adaptive evolution are probably among the most confused about cause and effect in the context of ecological, social, neurogenic, and socio-cognitive niche construction (i.e., nutrient-dependent pheromone-controlled adaptive evolution). Mutations do not cause adaptive evolution; they are not selected; they perturb it.