Seminar "Investigating granule cell functionality using automated olfactory conditioning" by Janine Reinert
Dr. Janine Reinert
University of Heidelberg
Title: Investigating granule cell functionality using automated olfactory conditioning
Olfaction, the sense of smell, is one of the most important sensory modalities for many organisms. The structure of the olfactory system has remained remarkably conserved across species, indicating that the precise anatomy is integral to the detection and discrimination of odours. Previous studies have shown that the connectivity of olfactory bulb mitral and granule cells plays a crucial role in odour discrimination in mice, yet several aspects of granule cell function remain unclear.
To investigate the impact of modified granule cell functionality on odour discrimination in rodents, we established a novel automated operant conditioning setup. This setup allowed us to train large (>20 animals) groups of mice on a go/no-go odour discrimination task with minimal experimenter interference.
We used this novel setup to investigate the impact of increased numbers of granule cells on odour discrimination. Towards this aim, a novel transgenic mouse line was used, in which the pool of neuronal stem cells can be temporarily increased. This approach resulted in an olfactory bulb specific increase of physiologically normal and functionally integrated granule cells. We were able to show that in mice harbouring an increased number of granule cells, the discrimination accuracy, but not the discrimination time of highly similar mixtures of two enantiomers is increased.
In a second approach aimed at reducing inhibitory feedback of granule cells onto mitral cells, we sought to eliminate T-type calcium channel expression specifically in granule cells. Thus we established a simultaneous shRNA-mediated triple knock-down of T-type calcium channels, delivered using stereotaxic AAV injection. Preliminary data suggests, that in mice with reduced T-type ion channel expression, discrimination of simple odours may already be affected.
These findings highlight the importance of granule cell-derived inhibitory input onto mitral cells for the discrimination of highly similar odour stimuli. Taking into account the subtle nature of the molecular modifications and the flexibility of the novel approach to behavioural phenotyping, these results clearly outline the path to a large-scale, systematic investigation into the limits of olfaction.
2013- Present University of Heidelberg (PhD advisor: Professor Thomas Kuner)