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How nerve cells discriminate olfactory clues

Whether different odours can be quickly discriminated depends on whether certain synapses in the brain are able to inhibit neuronal information processing. Scientists led by Professor Dr. Thomas Kuner at the Institute of Anatomy and Cell Biology at the Heidelberg Medical Faculty and Dr. Andreas Schäfer at the Max Planck Institute of Medical Research have shown that mice lacking a certain receptor in the olfactory bulb are able to discriminate similar odours more quickly than mice that have not been genetically manipulated and thus still possess the receptor. This behaviour is due to inhibitory circuits between neighbouring nerve cells.

Haldan K. Hartline, George Wald and Ragnar Granit were awarded the Nobel Prize 43 years ago for their discovery of the principle of lateral inhibition in the eye. The researchers from Heidelberg have now discovered that the olfactory system works according to the same principle, on both the molecular and the behavioural level. The results were recently published in the renowned journal “Neuron”.

In the nasal mucosa, odorous substances bind to the receptors of olfactory cells where they trigger nerve signals. These signals are then further processed in a part of the brain that is known as the olfactory bulb. Synaptic signals are converted into a specific electrical pattern that is transmitted to and recognised by the cerebral cortex and other brain areas.

Local inhibitory circuits specify the recognition of odours

Genetically modified granule cells of the olfactory bulb of mice. The nuclei of the granule cells were immunohistochemically stained with a red dye. Cells that express an additional protein following viral gene transfer appear in green and yellow (see arrows). © Institute of Anatomy and Cell Biology, University Hospital Heidelberg

Professor Kuner and his team have for the first time been able to show how the neuronal processing of olfactory clues directly affects the behaviour of experimental animals. "We specifically manipulated the processing of information in the olfactory bulb and measured the effect of these genetic manipulations on the basis of the animals' reaction time. This enabled us to show that the experimental animals were able to reliably discriminate mixtures of similar odours faster than non-manipulated mice, thanks to local inhibitory circuits," explains Professor Kuner.

The inhibition of the signals by way of interconnected nerve cells works like a filter that enhances strong stimuli and attenuates weak ones. This results in the fast and accurate discrimination of similar odours. The experimental animals reacted around 50ms quicker than non-manipulated mice. On the behavioural level, discrimination of similar odour mixtures was accelerated whilst learning and memory remained unaffected.

The scientists used a viral gene shuttle to introduce the enzyme Cre recombinase into the nerve cells of the olfactory bulb of young mice. The introduction of specific enzymatic recognition sites led to the removal of a specific gene region and resulted in the deletion of a receptor on the interconnected nerve cells. The specific manipulation of the gene led to the enhanced activity of inhibitory circuits. Had the researchers used knock-out mice in which the gene is deleted in the entire body, they would not have been able to observe the subsequent selective discrimination behaviour resulting from the manipulation of olfactory bulb granule cells. Using a sophisticated experimental set-up, the mice had to learn to recognise simple and complicated odour mixtures. Electrophysiological measurements, imaging methods and anatomic techniques were used to link stimulus similarity, neuronal processing time and discrimination behaviour to synaptic inhibition.

Literature:

NM Abraham, V Egger, DR Shimshek, R Renden, I Fukunaga, R Sprengel, PH Seeburg, M Klugmann, TW Margrie, AT Schaefer, T Kuner. Synaptic inhibition in the olfactory bulb accelerates odor discrimination in mice. Neuron, 2010, 65: 399-411 DOI 10.1016/j.neuron.2010.01.009

Further information:
Professor Dr. Thomas Kuner
Institute of Anatomy and Cell Biology
University of Heidelberg
Im Neuenheimer Feld 307
69120 Heidelberg
Tel.: +49 (0)6221 / 54 86 78
Fax: +49 (0)6221 / 54 49 52
E-mail: kuner(at)uni-heidelberg.de
Website address: https://www.gesundheitsindustrie-bw.de/en/article/press-release/how-nerve-cells-discriminate-olfactory-clues