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Localisation of neurotransmitters receptors raises fundamental questions in brain research

(Vienna, 3rd January 2011) The receptors for one of the most important neurotransmitters of the central nervous system were exactly localised and quantified for the first time in an international research project in association with the Medical University of Vienna. The results were surprising. They raised new questions and have not only put into question present assumptions about the mechanism of action of the transmitters, but have also opened new approaches to therapy.

GABA is the most important inhibiting synaptic transmitter of the central nervous system and plays a significant role in the regulation of the communication between nerve cells. Its “receptors“, the GABAA receptors, are therefore also the most frequent inhibiting receptors of the central nervous system. Its activation regulates several functions of the brain. Many clinically important drugs that affect these receptors amplify this effect. These drugs influence the sleep and the awakened state, the muscle tonus, regulate the excitability of the neurons and modulate anxiety, learning and memory.

An international workgroup headed by Prof. Peter Somogyi (MRC Anatomical Neuropharmacology Unit, Univ. Oxford, UK), who is also teaching as a visiting professor at the Centre of Brain Research of the Medical University of Vienna focussed on the localisation and frequency of GABA receptors and surprisingly identified approximately 60% of all GABAA receptor subunits in extrasynaptic receptors. “This raises the question whether and how this majority of extrasynaptic receptors differ from the synaptic receptors. Due to their frequency, the extrasynaptic receptors have to be re-evaluated and in future considered in all deliberations about the functioning of the brain“, says university Prof. Dr. Werner Sieghart, whose workgroup contributed significantly to the results achieved at the Vienna Centre of Brain Research.

Since it has to be assumed that the extrasynaptic receptors may also have other characteristics than the synaptic receptors, their pharmacological investigation and medical influence opens new therapy approaches. The significance of this discovery is also emphasised by the commented publication as cover story in the “European Journal of Neuroscience“:

Quantitative localisation of synaptic and extrasynaptic GABAA receptor subunits on hippocampal pyramidal cells by freeze-fracture replica immunolabelling
Yu Kasugai, Jerome D. Swinny, J. David B. Roberts, Yannis Dalezios, Yugo Fukazawa, Werner Sieghart, Ryuichi Shigemoto, Peter Somogyi
DOI: 10.1111/j.1460-9568.2010.07473.x