The role of calcium-activated chloride channels in olfactory signal processing

• Applicant: Professor Dr. Stephan Frings
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells ; Animal Physiology and Biochemistry ; Sensory and Behavioural Biology
• Term: from 2014 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 257313780

Ion channels mediate many different signaling processes in neurons, placing them in the focus of research into neuronal information processing. In the project proposed here, the question shall be addressed why the olfactory receptor neurons of vertebrates express calcium-activated chloride channels in their chemosensory cilia. The transduction from olfactory stimulus into electrical signals takes place in these cilia, and the chloride channels appear to play a central role in this process. According to the prevailing working hypothesis in olfactory research, the chloride channels are part of a cellular amplification mechanism which increases odor sensitivity. It is assumed that weak olfactory stimuli can only elicit electrical excitation if boosted by this amplification. New observation with mice, where chloride channels were genetically ablated, cast doubt on this notion, as the mice that lack the chloride channels can smell. The project proposed here is based on our recent discovery that the chloride channels in olfactory receptor neurons have a formerly unknown property: they inactivate. During odor stimulation, they open only briefly, then they close - even upon prolonged stimulation. This finding suggests that the time course of channel activity is critical for its physiological effect. Consequently, this project will primarily focus on dynamic aspects of signal processing in mice with and without chloride channels. Differences between wild-type mice and chloride-channel knockout mice will be examined by characterizing network activity in the olfactory bulb during repetitive, pulsatile stimulation in the frequency range of 1-12 Hz. Frequencies of 5-12 Hz correspond to the sniffing behavior of mice, an accelerated breathing pattern typical for explorative behavior and close inspection of odorous objects. An optogenetic approach will be chosen to achieve precise and reproducible stimuli. Light pulses are used for repetitive stimulation in mice which express channelrhodopsin in all olfactory receptor neurons. In parallel to these network studies, the mechanism of channel inactivation will be examined in molecular detail, as well as the regulation of inactivation on the level of olfactory receptor neurons. The goal of this project is to reveal the relation between chloride-channel activity and network activity and, hence, to arrive at an understanding of the role that chloride channels play in olfactory signal processing.

• DFG Programme: Research Grants
• Participating Person: Dr. Frank Möhrlen