Time Switch in the Brain Improves Sense of Smell

Summary: Researchers investigate how similar scents are differentiated.

Source: MDC.

Smells are a vital part of daily life: bad odors warn us off rotten food, and the aroma of a tasty meal stimulates salivation and digestion. Our sense of smell is closely linked to our autonomic nervous system, which controls the unconscious functions in our bodies as well as affecting our emotions.

A team led by Prof. Thomas J. Jentsch and postdoctoral researcher Kathrin Gödde of the Leibniz Institute for Molecular Pharmacology (FMP) and the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) collaborated with Swiss colleagues from the University of Geneva to find out more about this key aspect of perception.

The scientists wanted to find out how similar scents are differentiated – how our sense of smell is so finely tuned. A single note in the complex mixture of odors that make up the smell of fresh fish can reveal whether it is still edible, for example. At the core of sensory perception are the odor molecules in the smells that we inhale.

Like a key in a lock, an odor molecule fits to the receptor on the surface of the sensory cells in the olfactory mucosa. Stimulation causes these olfactory cells to send signals to the brain’s olfactory bulb, where mitral and tufted cells (M/T cells) process them and forward them to other areas of the brain in a kind of Morse code.

Each olfactory cell carries only one kind of receptor, which is specific to particular odor molecules and is hard wired to one region in the olfactory bulb. In this way, a spatial signature for a smell is generated in the olfactory bulb. However, the team of scientists showed that to represent the very small differences between smells, time-dependent coding is also essential.

We can differentiate between similar odor molecules because of a subtle modulation in the sequence of signals in the Morse code; the formerly synchronous cells sending the codes are thrown out of step. Each odor therefore has an individual, time-dependent signal pattern. Up to now, scientists had assumed that inhibiting signals delivered to the M/T cells change their state of excitation, which in turn influences the temporal sequence of the Morse codes and help discriminate similar odors. The hypothesis was still ambiguous and was the object of the research team’s study.

Image shows Kcc2 in a mouse's olfactory bulb.

The mitral cells are in the middle region is shown. Plenty of Kcc2, marked in green, is present. Nuclei are stained in blue. NeuroscienceNews.com image is credited to Kathrin Gödde/FMP/MDC.

The scientists reduced the inhibiting signals that the M/T cells received from neighboring cells in the olfactory bulbs of mice by genetically deactivating the ion transporter Kcc2 in specifically these kinds of cells. This severely changed the electrical balance of the M/T cells, meaning that they virtually ceased to receive any inhibiting signals.

In the behavioral tests, the mice that had been genetically altered in this way could still differentiate between odor molecules that were clearly different – the inhibiting signals therefore appear to have no influence on the general ability to smell. Yet the mice were no longer able to distinguish between odor mixtures with slightly different ratios of the same odors. In addition, they could not differentiate between molecules that are very similar in their chemical structure such as (+) limonene (lemon scent) and (-) limonene (turpentine scent).

The researchers in Geneva provided an explanation for this phenomenon. They studied the electrical characteristics of the M/T cells in living mice. When the inhibiting signals acting on M/T cells were suppressed, the neurons were more strongly excited and in addition the creation of the Morse code for different smells was impaired. As a result, the odor-specific signatures were more similar and thus more difficult to distinguish.

Kathrin Gödde says: “Our results prove that time-dependent pattern formation in the signals of M/T cells, with the help of neuronal inhibition, is extremely important for differently representing similar odors in the brain and thereby for discrimination between them. This is the first time this has been shown with such clarity.”

About this neuroscience research article

Funding: This work was funded by the German Research Foundation (DFG) and the NeuroCure Cluster of Excellence, the European Research Council (ERC), the Swiss National Science Foundation, and a PhD Fellowship of the Boehringer Ingelheim Fonds.

Source: Vera Glaßer – MDC
Image Source: This NeuroscienceNews.com image is credited to Kathrin Gödde/FMP/MDC.
Original Research: Full open access research for “Disruption of Kcc2-dependent inhibition of olfactory bulb output neurons suggests its importance in odour discrimination” by Kathrin Gödde, Olivier Gschwend, Dmytro Puchkov, Carsten K. Pfeffer, Alan Carleton and Thomas J. Jentsch in Nature Communications. Published online July 8 2016 doi:10.1038/ncomms12043

Cite This NeuroscienceNews.com Article
MDC. “Time Switch in the Brain Improves Sense of Smell.” NeuroscienceNews. NeuroscienceNews, 8 July 2016.
<http://neurosciencenews.com/mt-cells-olfaction-neuroscience-4644/>.
MDC. (2016, July 8). Time Switch in the Brain Improves Sense of Smell. NeuroscienceNews. Retrieved July 8, 2016 from http://neurosciencenews.com/mt-cells-olfaction-neuroscience-4644/
MDC. “Time Switch in the Brain Improves Sense of Smell.” http://neurosciencenews.com/mt-cells-olfaction-neuroscience-4644/ (accessed July 8, 2016).

Abstract

Disruption of Kcc2-dependent inhibition of olfactory bulb output neurons suggests its importance in odour discrimination

Synaptic inhibition in the olfactory bulb (OB), the first relay station of olfactory information, is believed to be important for odour discrimination. We interfered with GABAergic inhibition of mitral and tufted cells (M/T cells), the principal neurons of the OB, by disrupting their potassium-chloride cotransporter 2 (Kcc2). Roughly, 70% of mice died around 3 weeks, but surviving mice appeared normal. In these mice, the resulting increase in the intracellular Cl− concentration nearly abolished GABA-induced hyperpolarization of mitral cells (MCs) and unexpectedly increased the number of perisomatic synapses on MCs. In vivo analysis of odorant-induced OB electrical activity revealed increased M/T cell firing rate, altered phasing of action potentials in the breath cycle and disrupted separation of odour-induced M/T cell activity patterns. Mice also demonstrated a severely impaired ability to discriminate chemically similar odorants or odorant mixtures. Our work suggests that precisely tuned GABAergic inhibition onto M/T cells is crucial for M/T cell spike pattern separation needed to distinguish closely similar odours.

“Disruption of Kcc2-dependent inhibition of olfactory bulb output neurons suggests its importance in odour discrimination” by Kathrin Gödde, Olivier Gschwend, Dmytro Puchkov, Carsten K. Pfeffer, Alan Carleton and Thomas J. Jentsch in Nature Communications. Published online July 8 2016 doi:10.1038/ncomms12043

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