The context in which a sensory experience occurs can strongly influence whether it is perceived aspleasurable or aversive. In Drosophila, the volatile lipid pheromone cis-vaccenyl acetate (cVA) is producedby males and transferred to females during mating. When presented on eggs laid at food sources, it acts asan attractant. When presented on a mature female, it causes both instantaneous and long-term suppressionof male courtship. In both of these situations the presence of another odor dictates the behavioral responseto cVA. Our overall goal is to understand how olfactory context can change the immediate effects of apheromone and lead to long-term changes in behavior. In this grant we will define the circuitry that isinvolved in sensing cVA and courtship-stimulating pheromones and identify the mechanisms that integratepheromone signals to create appropriate modulation of courtship initiation. We will use genetically encodedprobes of neuronal activity to assess the contribution of local antenna! lobe circuits to association of thesecues. These experiments will provide insights into how odor information is processed and into howolfacotrymemory is formed. Research in invertebrate model systems has arguably been the driver of the field ofmolecular memory in mammals. The high degree of structural and molecular conservation in the olfactorysystem and in mechanisms of learning makes work on olfactory plasticity in Drosophila germane to humanhealth for the many developmental and acquired conditions that affect learning and memory.
Specific aims are:1. Define the olfactory neuron inputs that are required for sensing cVA and courtship-stimulating femalepheromones.2. Investigate the mechanisms of association between stimulatory pheromones and cVA in the antennallobe.3. Investigate the mechanisms of context integration in the antennal lobe.4. Characterize the role of dTrpAl, a non-specific cation channel, in suppression of male-male courtship(collaboration with Garrity Lab).The olfactory system of Drosophila and the molecular basis of learning in this organism are highlyhomologus to that of humans. Understanding of the cellular mechnaism of olfactory learning in this organismwill provide valuable information that can be used in designing therapeutics for human disorders of cognitionsuch as Alzheimer's disease and mental retardation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
2P01NS044232-06
Application #
7387951
Study Section
Special Emphasis Panel (ZNS1-SRB-B (03))
Project Start
Project End
Budget Start
2007-08-15
Budget End
2008-07-31
Support Year
6
Fiscal Year
2007
Total Cost
$294,817
Indirect Cost
Name
Brandeis University
Department
Type
DUNS #
616845814
City
Waltham
State
MA
Country
United States
Zip Code
02454
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