Odorant receptor complexes in olfactory cilia and axons
Final Report Abstract
Understanding the functional implications of odorant receptors is still a key for unraveling the mechanisms underlying the sense of smell; this is particularly true for the ligand specificity of particular receptor types. In search for compounds which can activate receptors of the unique OR37 subfamily, we have established a novel screening approach which has made it possible to deorphanized some of the OR37 receptors. It was found that these receptors are activated by compounds which are not considered as typical odorous molecules, but rather are long-chain aliphatic aldehydes with a chain length of 15 to 17 C-Atoms, so-called fatty aldehydes. It turned out that each of the three analysed OR37 receptor subtypes showed a strong preference for an aldehyde with a particular chain length; moreover, the corresponding alkane, alcohol or acid did not induce any activation. Thus, each of the OR37 receptors displays a significant degree of ligand specificity, a feature, which is quite unusual for general odorant receptors. Towards an understanding where the chemosensory information provided by OR37 ligands may be processed in higher brain centers tracing experiments were performed to explore the neuronal connectivity. Employing an OR37C-specific transsynaptic tracing approach revealed that projection neurons from the OR37C glomerulus were connected to a specialized region of the amygdala, and also to distinct nuclei in the hypothalamus; however, no projections to the classical olfactory cortex were found. These results indicate an atypical connectivity of the OR37C glomerulus to higher brain centers. Since the OR37 receptor family is only present in mammals, the search for natural sources of OR37 ligands was concentrated on conspecifics. The current findings indicate that some of the potential ligands for the OR37 receptors are generated and released by distinct skin glands. Altogether, the results of the project support the concept that the olfactory OR37 subsystem may play an important role in the chemosensory based social communication of mammals.
Publications
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(2012). Connectivity from OR37 expressing olfactory sensory neurons to distinct cell types in the hypothalamus. Front. Neural Circuits 6, 84
Bader, A, Klein B, Breer, H, and Strotmann J
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(2012). Mammalian-specific OR37 receptors are differentially activated by distinct odorous fatty aldehydes. Chem. Senses 37, 479-493
Bautze V, Bär R, Fissler B, Trapp M, Schmidt D, Beifuss U, Bufe B, Zufall F, Breer H, and Strotmann J
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(2012). Untypical connectivity from olfactory sensory neurons expressing OR37 into higher brain centers visualized by genetic tracing. Histochem. Cell Biol. 137, 615-628
Bader A, Breer H and Strotmann J
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(2014). Identification of a natural source for the OR37B ligand. Chem. Senses 39, 27-38
Bautze V, Schwack W, Breer H, and Strotmann J