Neuronal mechanisms of pheromone sensing
Final Report Abstract
Chemosensory cues influence sexual behavior and reproductive physiology, but how the olfactory system influences specific output neurons in the brain mediating these effects is not understood. The main goal of this tandem project was to start to dissect the underlying neural circuitry focusing on the newly-identified gonadotropin releasing hormone (GnRH) receptor neurons and their role in reproductive behavior. The vomeronasal system is of particular importance to female mice in modulating reproduction. GnRH signaling is the critical nexus of the neuronal network controlling fertility in the vertebrate brain and has been implicated as a target of olfactory processing. We identified GnRH receptor neurons in brain areas that receive vomeronasal input using genetic labeling capitalizing on newly generated reporter mice we developed during the SPP funding period. We then started to explore their physiological activity at different phases of the female reproductive cycle. We published several reports on this topic demonstrating how GnRH target neurons in the brain are affected by changes in plasma GnRH levels during ovulation. Our work has laid the foundation to start investigating olfactory and reproductive processing in the brain. We also collaborated with several other PIs within the SPP network, e.g. analyzing the peptidome in mouse urine and on questions related to immune peptides and receptors within the vomeronasal system.
Publications
- (2011) Genetic identification of GnRH receptor neurons: a new model for studying neural circuits underlying reproductive physiology in the mouse brain. Endocrinology 152: 1515-1526
Wen S, Götze IN, Mai O, Schauer C, Leinders-Zufall T, Boehm U
(See online at https://doi.org/10.1210/en.2010-1208) - (2012) Genetic labeling of tas1r1 and tas2r131 taste receptor cells in mice. Chem Senses 37, 897-911
Voigt A, Hübner S, Lossow K, Hermans-Borgmeyer I, Boehm U, Meyerhof W
(See online at https://doi.org/10.1093/chemse/bjs082) - (2013) Mouse urinary peptides provide a molecular basis for genotype discrimination by nasal sensory neurons. Nat Commun 4, 1616
Sturm T, Leinders-Zufall T, Mecek B, Walzer M, Jung S, Pömmerl B, Stevanovic S, Zufall F, Overath P, Rammensee HG
(See online at https://doi.org/10.1038/ncomms2610) - (2013) Taste responses in mice lacking taste receptor subunit T1R1. J Physiol 591, 1967-1985
Kusuhara Y, Yoshida R, Ohkuri T, Yasumatsu K, Voigt A, Hübner S, Maeda K, Boehm U, Meyerhof W, Ninomiya Y
(See online at https://doi.org/10.1113/jphysiol.2012.236604) - (2014) A family of nonclassical class I MHC genes contributes to ultrasensitive chemodetection by mouse vomeronasal sensory neurons. J Neurosci 34, 5121-5133
Leinders-Zufall T, Ishii T, Chamero P, Hendrix P, Oboti L, Schmid A, Kircher S, Pyrski M, Akiyoshi S, Khan M, Vaes E, Zufall F, Mombaerts P
(See online at https://doi.org/10.1523/JNEUROSCI.0186-14.2014) - (2014) TRP channels in reproductive (neuro)endocrinology. In: Handbook of Experimental Pharmacology: Mammalian Transient Receptor Potential (TRP) Cation Channels, eds Nilius B & Flockerzi V (Springer), Vol 223: 1107-1118
Leinders-Zufall T, Boehm U
(See online at https://doi.org/10.1007/978-3-319-05161-1_16) - (2015) Hypothalamic gonadotropin-releasing hormone (GnRH) receptor neurons fire in synchrony with the female reproductive cycle. J Neurophysiol 114, 1008-1021
Schauer C, Tong T, Petitjean H, Blum T, Peron S, Mai O, Schmitz F, Boehm U, Leinders- Zufall T
(See online at https://doi.org/10.1152/jn.00357.2015) - (2015) TAS2R bitter taste receptors regulate thyroid function. FASEB J 29, 164-172
Clark AA, Dotson CD, Elson AE, Voigt A, Boehm U, Meyerhof W, Steinle NI, Munger SD
(See online at https://doi.org/10.1096/fj.14-262246) - (2015) Transsynaptic tracing from taste receptor cells reveals local taste receptor gene expression in gustatory ganglia and brain. J Neurosci 35, 9717-9729
Voigt A, Bojahr J, Narukawa M, Hübner S, Boehm U, Meyerhof W
(See online at https://doi.org/10.1523/JNEUROSCI.0381-15.2015) - (2016) A sensor for low environmental oxygen in the mouse main olfactory epithelium. Neuron 92, 1-8
Bleymehl K, Pérez-Gómez A, Omura M, Moreno-Pérez A, Macias D, Bai Z, Johnson RS, Leinders-Zufall T, Zufall F, Mombaerts P
(See online at https://doi.org/10.1016/j.neuron.2016.11.001)
