The Investigation of the Role of the TRPV Channel OSM-9 in Olfactory Long-term Memory Formation

University Of California, San Francisco, San Francisco CA

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Abstract

Project Summary/Abstract Memory is one of the most important abilities of the brain. It is defined as an alteration in behavior from an experience. For example, the C. elegans nematode will downregulate its chemotactic response to an innately attractive odor if it is not paired with food1. This process is termed olfactory classical conditioning. Through spaced training with this odor, C. elegans will maintain this memory of the odor for a prolonged period of time, akin to long-term memory formation. Although TRP channels are classically thought of as primary sensory receptors, intriguingly, it has been reported that the OSM-9 TRPV (vanilloid) channel protein is required for odor classical conditioning2, and a new role has been discovered for it in long-term memory formation (LTM). Nevertheless, the mechanisms that regulate TRPV-mediated LTM remain a mystery. The goal of the proposed research is to uncover the mechanism of OSM-9/TRPV-mediated LTM in the olfactory sensory circuit of C. elegans. The proposed aims will test the hypothesis that OSM-9 functions in specific cells in the olfactory circuit by facilitating Ca2+ flux in the olfactory neurons to mediate odor long-term memory in adult C. elegans animals. TRP channels are known to be monovalent and divalent cation-permeable channels3. Previous research shows that OSM-9 and Ca2+ are the most downstream components in the conditioning-promoting pathway4,5. Thus, OSM-9 may cause an influx of Ca2+ into the olfactory sensory neurons or potentially other neurons within the circuit to promote LTM. The following specific aims will extend these studies and test in aim 1: the spatiotemporal requirements for OSM-9-mediated LTM after long-term odor exposure and in aim 2: the mechanism of OSM-9-mediated Ca2+ dynamics in promoting olfactory LTM. These studies will be accomplished through the use of microscopy, functional imaging, behavioral analysis, and genetic techniques. TRP channels are well studied in their ability to sense noxious stimuli3,6, yet they are also implicated in many diseases and disorders that limit neural plasticity, including Parkinson?s disease, Alzheimer?s disease, stroke, and sense disorders including anosmia. The proposed studies will elucidate the role of TRP channels in neural plasticity, specifically, in olfactory long-term memory formation. These findings will broaden our knowledge of TRP channel function as a mediator of plasticity, which could potentially aid in understanding and treating the many diseases and disorders caused by TRP channel dysfunction.