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MULTIPLE SIGNAL TRANSDUCTION EVENTS AND MODULATION OF OLFACTORY RESPONSES IN MOUSE OLFACTORY SENSORY NEURONS
Title
MULTIPLE SIGNAL TRANSDUCTION EVENTS AND MODULATION OF OLFACTORY RESPONSES IN MOUSE OLFACTORY SENSORY NEURONS
Creator
Yu, Yiqun
Date
2012-04-30, 2012-07
Description
In the mammalian olfactory system, one olfactory sensory neuron (OSN) expresses a single olfactory receptor (OR) gene. I studied two subsets...
Show moreIn the mammalian olfactory system, one olfactory sensory neuron (OSN) expresses a single olfactory receptor (OR) gene. I studied two subsets of mouse OSNs, hereafter refered to as Ho-OSNs and AB-OSNs, in intact mouse olfactory turbinates using calcium imaging. Both of Ho-OSNs and AB-OSNs were located in the most ventral olfactory receptor zone. Ho-OSNs were specifically responsive to 2-heptanone (Ho), heptaldehyde (H) and cis-4-heptenal (cH). Dose-dependent analysis indicated that their responses to individual odorant was saturated within one logarithm unit of concentrations, a typical characteristic of isolated OSNs. Binary mixture and crossadpatation studies showed that these three odorants bound to the same binding sites in Ho-OSNs. However, these three structurally similar odorants activated distinct signaling pathways in Ho-OSNs. In detail, 2-heptanone-evoked intracellular calcium elevation was mediated by AC-cAMP signaling, while heptaldehyde triggered the PLC-DAG pathway. The cis-4-heptenal-evoked [Ca2+]i increases resulted from a combination of cAMP mediated activation and suppression involving PLC signaling. Furthermore, the PLCmediated intracellular calcium alteration was independent of IP3 signaling. A further complexity is that these olfactory receptors were able to interact with other types of Gprotein coupled receptors (GPCRs), such as purinergic receptors. I determined that both the P2X3 and P2Y2 receptor subtypes were expressed in Ho-OSNs. Application of purinergic agonists elevated [Ca2+]i increases in Ho-OSNs. It was discovered that the ATP-induced calcium response required either intracellular or extracellular calcium, while depletion of intracellular calcium stores blocked the UTP-evoked [Ca2+]i increases. Purinergic agonists were able to modulate the odor response in Ho-OSNs, and purinergic antagonist experiments showed that modulation of heptaldehyde-induced calcium responses was due to activation of P2X3 receptor subtypes while heptanone-induced calcium responses was not. Although AB-OSNs were found adjacent to Ho-OSNs, they had complete separate response profiles. AB-OSNs were sensitive to acetophenone (Ace) and benzaldehyde (Ben). In AB-OSNs, both acetophenone and benzaldehyde activated the PLC signaling pathway. Pharmacological characterization indicated that in AB-OSNs, P2X1 and P2Y2 receptors were present, which is different from that in Ho-OSNs. P2X and P2Y agonists modulated odorant responses in AB-OSNs. Purinergic signaling differentially regulated the various odorant responses in AB-OSNs. The acetophenoneevoked [Ca2+]i increases were negativly modulated through activation of the P2Y2 receptor, while the calcium response induced by benzaldehyde was modulated by P2X1 receptor activation. Collectively, these studies suggest that a complex signaling mechanism exists in OSNs, which has important implications for understanding the mechanism of information process in the olfactory system.
Ph.D. in Biology, July 2012
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