Primary sensory neuropils perform the initial decomposition of complex sensory signals in the environment. Beyond this basic function, sensory circuits also must discriminate perceptual objects under a wide range of different ambient conditions, including situations that may involve the formation of learned associations with other sensory cues. We need a more thorough understanding of how sensory networks are modulated by inputs from other brain regions in order to gain better insight into the mechanisms that help stabilize internal perceptual states in the brain. A deeper analysis of sensory-circuit plasticity is crucial for the development of more effective therapies for sensory brain disorders and treatments for the aberrant sensations that often accompany mental illness. Using the olfactory system of an experimentally favorable model, Manduca Sexta, we now have evidence that a learning-based reorganization of odor-evoked network responses takes place in the antennal lobe, the structural and functional analog of the mammalian olfactory bulb. What mechanisms underlie this unexpected network plasticity in the pdmary olfactory center? In order to understand the nature of this modulation, research must be focused on the structural and functional organization of the olfactory circuits that exhibit these changes, and more must be learned about the complex interplay among multiple neurotransmitter systems that helps to reshape the spatiotemporal representations of olfactory stimuli with experience. In Manduca, four candidate amine transmitters have been localized to separate neurons in the glomeruli of the antennal lobe, making this an ideal system to examine the modulatory roles of biogenic amines in olfactory-information coding. This project will build on a strong foundation of experience with this experimentally-favorable model and will seek to characterize the regulatory roles of aminergic modulation in reshaping odor representations during olfactory conditioning. We will employ a strongly multidisciplinary approach, combining single-unit and neural-ensemble recording & anatomy with neuropharmacology and behavioral bioassays to study the roles of amines in regulating the formation, storage, and recall of offactory memories during the conditioning process. Our understanding of the functional meaning of plasticity in early olfactory processing is still rudimentary, and the proposed studies aim to test the hypothesis that centrifugal aminergic modulation plays a key role in olfactory plasticity and the regulation of adaptive behavior.
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