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Olfactory tubercle circuits involved in odor valence assignment

嗅结节回路参与气味价分配

基本信息

批准号：
9756635
负责人：
Nuné Martiros
金额：
$ 6.37万
依托单位：
HARVARD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-01 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9756635
关键词：
Anatomy Association Learning Auditory Axon Basal Ganglia Behavior Behavioral Behavioral Assay Behavioral Paradigm Bilateral Brain Brain region Calcium Chronic Complex Corpus striatum structure Development Discrimination Disease Dopamine Dopamine D1 Receptor Dopamine D2 Receptor Dopamine Receptor Due Process Emotional Emotions Environment Evolution Exhibits Health Human Hydroxydopamines Image Learning Lesion Modality Mus Neurons Neurosciences Odors Olfactory Pathways Olfactory tubercle Outcome Output Positioning Attribute Process Psychological reinforcement Research Rewards Role Route Sensory Signal Transduction Smell Perception Stimulus Stream Structure Synapses System Testing Training Transgenic Organisms Ventral Striatum Ventral Tegmental Area Virus Water auditory stimulus base classical conditioning experience imaging approach learning outcome lens microendoscopy mouse model neuron development novel olfactory bulb olfactory stimulus preference prevent receptor response sensory stimulus sham surgery sound two photon microscopy

项目摘要

Project Summary How sensory stimuli acquire emotional tags 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 this 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 conserved stream of olfactory information to limbic brain regions like the olfactory tubercle may be the basis of a proposed exceptional 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 (1) the processes underlying 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.

项目总结