Olfactory tubercle circuits involved in odor valence assignment

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How sensory stimuli acquire valence based on behavioral experience is a subject of vital importance in neuroscience, but has been difficult to study due to the complex brain circuits involved in the process. I propose that olfaction may be an ideal system in which to interrogate this question due to the direct interface of olfactory bulb projections and dense dopaminergic input in a ventral basal ganglia structure, the olfactory tubercle. Furthermore, this evolutionarily preserved direct interface of olfactory and reward- prediction information, may be the basis of a proposed unique capacity of odors to evoke positive or negative emotional responses. I plan to first dissect the function of olfactory tubercle circuits in odor- valence assignment in a classical conditioning task by using microendoscopy to perform calcium activity imaging of single D1-type or D2-type dopamine receptor expressing neurons in the olfactory tubercle. I will then ablate dopamine terminals in the olfactory tubercle locally with the use of 6-hydroxydopamine, and assess the changes in the odor and outcome evoked activity in the same neuronal types in the absence of dopamine input. Secondly, I will develop a novel behavioral assay in order to test the hypothesis that learned odor associations result in odor preferences that are uniquely strong as compared to stimulus- outcome associations with stimuli of another sensory modality (audition). To do so, I will first identify odor and sound stimuli of similar discriminability for mice and then use these stimuli in a classical conditioning task. After stimulus-outcome training, the preference of the mice for the stimuli used in classical conditioning will be assessed in a preference test. Finally, I will test the causal role of the olfactory tubercle in odor-outcome learning and in the development of odor preferences with the use of bilateral lesions of the olfactory tubercle. Together, the proposed research is likely to contribute significantly to our understanding of the processes underlying (1) valence assignment to sensory stimuli, (2) the functional circuit mechanisms of the olfactory tubercle, an understudied brain region, and (3) the behavioral phenomenon of odor-evoked emotional responses and associated brain circuits.