Mechanistic basis of vomeronasal pump operation

Tue-P1-022

Presented by: Christoph Hamacher

Christoph Hamacher ¹, Rudolf Degen ¹, Melissa Franke ¹, Victoria K. Switacz ¹, David Fleck ¹, Raghu R. Katreddi ², Martin Strauch ³, Nao Horio ⁴, Enno Hachgenei ⁵, Stephen D. Liberles ⁴, Jeroen Kalkman ⁶, Dorit Merhof ³, Paolo E. Forni ², Geraldine Zimmer-Bensch ⁷, Yoram Ben-Shaul ⁸, Marc Spehr ¹

¹ Department of Chemosensation, Institute for Biology II, RWTH Aachen University, Aachen, Germany, ² Department of Biological Sciences, University at Albany, State University of New York, Albany, NY, USA, ³ Institute of Imaging and Computer Vision, RWTH Aachen University, 52074 Aachen, Germany, ⁴ Howard Hughes Medical Institute, Department of Cell Biology, Harvard Medical School, Boston, MA, USA, ⁵ Department of Production Metrology, Fraunhofer Institute for Production Technology, Aachen, Germany, ⁶ Department of Imaging Physics, Delft University of Technology, Delft, The Netherlands, ⁷ Department of Neuroepigenetics, Institute for Biology II, RWTH Aachen University, Aachen, Germany, ⁸ Department of Medical Neurobiology, Institute for Medical Research Israel Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.

In most mammals, the vomeronasal organ (VNO) is crucial for the detection of semiochemicals, which trigger a wide range of innate behaviors. The VNO is a blind-ending cylindrical structure with a mucus-filled lumen, from where sensory neurons can detect solved stimuli. Few physiological studies have addressed vomeronasal stimulus uptake. Accordingly, fundamental mechanisms underlying vomeronasal operation remain elusive. Here, we investigate the molecular and cellular mechanisms that control stimulus uptake into the mouse VNO. Using both antibody staining and genetic cell labeling, we demonstrate that the lateral non-sensory VNO tissue is largely built by smooth muscle cells (SMCs), which are innervated by cholinergic and / or adrenergic fibers. Superresolution and fluorescence lifetime imaging microscopy reveal two SMC populations with longitudinal and circular orientation. Stimulation of acute coronal VNO slices from mice expressing GCaMP6f in SMCs, led to either elevated calcium levels and strong contractions in the lateral non-sensory tissue upon noradrenaline (NA) stimulation or elevated calcium levels in select SMCs located close to the lumen upon acetylcholine (ACh) exposure. NA-mediated contractions are also observed in tissue slices from juvenile mice that retain the cartilaginous VNO capsule. With this support structure intact, NA stimulation results in expansion of the VNO lumen. This effect is also detected in intact skull post mortem preparations using optical coherence tomography. Together, these morphological and functional data suggest that vomeronasal pumping is mediated by antagonistic SMC types, selectively activated by NA or ACh, respectively.