Olfactory tubercle circuits involved in odor valence assignment

嗅结节回路参与气味价分配

• 批准号: 10397941
• 负责人: Nuné Martiros
• 金额: $ 0.25万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10397941
• 关键词: Association Learning; Auditory; Basal Ganglia; Behavioral; Behavioral Assay; Behavioral Paradigm; Bilateral; Brain; Brain region; Calcium; Chronic; Complex; Development; Discrimination; Disease; Dopamine; Dopamine D1 Receptor; Dopamine D2 Receptor; Dopamine Receptor; Emotional; Emotions; Evolution; Exhibits; Health; Human; Image; Lesion; Modality; Mus; Neurons; Neurosciences; Odors; Olfactory tubercle; Outcome; Oxidopamine; Process; Research; Rewards; Role; Sensory; Site; Smell Perception; Stimulus; Structure; System; Testing; Training; Transgenic Organisms; Virus; Water; auditory stimulus; base; classical conditioning; dopaminergic neuron; experience; imaging approach; learning outcome; lens; microendoscopy; mouse model; neuron development; neuronal circuitry; novel; olfactory bulb; olfactory stimulus; preference; preservation; prevent; receptor; response; sensory stimulus; sound

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.

感官刺激如何获得基于行为经验的效价是一个至关重要的主题， 神经科学，但一直很难研究，由于复杂的大脑回路参与的过程。我 提出嗅觉可能是一个理想的系统，在其中询问这个问题，由于直接 腹侧基底神经节结构中嗅球投射和密集多巴胺能输入的界面， 嗅结节此外，这种在进化上保留的嗅觉和奖励的直接界面- 预测信息，可以是所提出的气味的独特能力的基础，以唤起积极的或 消极的情绪反应。我计划首先解剖嗅结节回路在气味中的功能- 在经典条件反射任务中使用显微内窥镜检查进行钙活性的效价分配 在嗅结节中单个D1型或D2型多巴胺受体表达神经元的成像。我 然后使用6-羟基多巴胺局部切除嗅结节中的多巴胺末梢， 并评估气味和结果诱发活动的变化，在相同的神经元类型的情况下， 多巴胺的输入。其次，我将开发一种新的行为测定法，以检验以下假设： 习得的气味关联导致气味偏好与刺激相比是唯一强烈的， 结果与另一种感觉方式（听觉）刺激的关联。为此，我将首先确定 气味和声音刺激相似的辨别力的小鼠，然后使用这些刺激在一个经典的 条件反射任务在刺激-结果训练后，小鼠对用于刺激的偏好 将在偏好测试中评估经典条件反射。最后，我将测试嗅觉的因果作用， 结节在气味结果学习和使用双侧气味偏好发展中的作用 嗅结节的病变。总之，拟议的研究可能会大大有助于 我们对以下过程的理解：（1）感觉刺激的效价分配，（2） 功能电路机制的嗅结节，研究不足的大脑区域，和（3） 气味引起的情绪反应和相关的大脑回路的行为现象。