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How our behavior leaves traces in the brain

Learning and behavioral processes affect and alter the nerve cell networks in the brain. Prof. Peter Scheiffele’s research group, from the Biozentrum at the University of Basel, has identified a new mechanism by which neurons can modify and re-arrange their connections. Focusing on a component of neuronal junctions, called neurexin, they demonstrated that neurons vary the nature of their connections in response to signals. These findings, which have been published in the journal Cell, provide not only an insight into the basic processes of neuronal network development but also bear relevance for neuronal disorders such as autism and schizophrenia.

The group of the neurobiologist Prof. Peter Scheiffele has been able to elucidate a new mechanism by which nerve cells (neurons) alter the formation of their networks in the brain depending on neuronal signals. These findings demonstrate how neuronal activity during the development of the nervous system or during a learning process directly affects the nature of the connections in the nervous system.

Neurexin - variants alter the nature of neuronal connections

The nervous system is a network of a multitude of neurons, that are connected to each other through so-called synapses. Since synapses transmit nerve impulses from one neuron to the next, the structure, number and nature of the synapses are of crucial importance for information transmission. In this process, the membrane protein neurexin bridges neighboring cells through specific binding partners, creating a connection between the two neurons.

A unique feature of neurexin is that it can be found in about 3000 variants, which bind to specific receptors in neighboring cells. The production of different neurexins occurs mainly through so-called alternative RNA splicing. During this process, depending on the conditions, various neurexins with differing binding characteristics are produced. How neurons regulate the splicing process in order to produce the appropriate neurexin derivative was not understood.

Altered behavior – altered neuronal connections

Scheiffele‘s group has been able to show that the activation of neurons affects alternative splicing through the action of a specific RNA binding protein. This binding protein determines which neurexin variant will be produced. Thereby, in response to a neuronal signal neurons are able to couple with neighboring cells that previously were not accessible to them. The neuronal connections can thus be modified through changes in neuronal activity.

“This new mechanism for regulation provides an insight into how our perceptions and behavior directly modify the neuronal network in the brain“, explained Scheiffele, adding “For example, if one learns to play a musical instrument, and trains the movements of the hand, the brain stores this information through the appropriately formed nerve cell connections.“

Given the large number of neurexin variants, the research group would like to concentrate in the future on the effects of further neurexin forms on the formation and function of neuronal networks. As modifications in neurexins are seen in patients with autism or schizophrenia, the research findings could also contribute to a better understanding of these disorders.

Original article:
Takatoshi Iijima, Karen Wu, Harald Witte, Yoko Hanno-Iijima, Timo Glatter, Stéphane Richard, Peter Scheiffele (2011): SAM68 regulates neuronal activity-dependent alternative splicing of Neurexin-1. Cell, Published online 22 December, 2011.

Contact: Communications, Heike Sacher