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.

Public Health Relevance

/Statement of Public Health Relevance Transient receptor potential (TRP) channels are proteins best understood in their role as sensors of harmful environmental stimuli, yet they have a less understood role in regulating neural plasticity?a fundamental process in the brain that governs information storage and adaptation to environmental cues. Indeed, a vast array of neurological diseases, including Alzheimer's disease, Parkinson's disease, as well as sense disorders, result from defects in TRP function, with affected individuals exhibiting decreased neural plasticity. This study aims to elucidate how TRP protein functions at the molecular level to promote plasticity and memory formation, which may lead to future treatments for TRP-mediated diseases and disorders, as well as increase our understanding of learning and memory.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31DC014921-02
Application #
9555796
Study Section
Special Emphasis Panel (ZDC1)
Program Officer
Rivera-Rentas, Alberto L
Project Start
2017-09-01
Project End
2019-11-20
Budget Start
2018-11-21
Budget End
2019-11-20
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Anatomy/Cell Biology
Type
Schools of Dentistry/Oral Hygn
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118