Olfactory tubercle circuits involved in odor valence assignment

项目摘要 感官刺激如何获得基于行为经验的情感标签是一个至关重要的主题， 在神经科学中的重要性，但由于涉及复杂的大脑回路， 这个过程我认为，嗅觉可能是一个理想的系统，在其中询问这个问题，由于 腹侧基底神经节内嗅球投射与多巴胺能神经传入的直接界面 结构，嗅结节。此外，这种进化上保守的嗅觉流 信息的边缘脑区，如嗅结节可能是一个拟议的例外的基础， 气味引起积极或消极情绪反应的能力。我计划首先剖析 经典条件反射任务中气味-效价分配的嗅结节回路 显微内窥镜检查，以进行单个D1型或D2型多巴胺受体的钙活性成像 嗅结节中的表达神经元。然后我会切除嗅觉区的多巴胺末梢 结节局部使用6-羟基多巴胺，并评估气味和结果的变化 在没有多巴胺输入的情况下，在相同的神经元类型中诱发活动。第二，我将开发一个 一种新的行为测定法，以检验习得的气味关联导致气味 与刺激-结果关联相比， 另一种感官形式（听觉）。为了做到这一点，我将首先确定气味和声音刺激类似 辨别能力，然后在经典条件反射任务中使用这些刺激。刺激后-结果 训练中，小鼠对经典条件反射中使用的刺激物的偏好将在一个实验中评估。 偏好测试最后，我将测试嗅觉结节在气味结果学习中的因果作用， 在气味偏好的发展与使用双侧病变的嗅结节。 总之，拟议的研究可能会大大有助于我们理解（1） 感觉刺激的配价过程，（2）感觉刺激的功能电路机制， 嗅结节，一个研究不足的大脑区域，和（3）气味诱发的行为现象， 情绪反应和相关的大脑回路。

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.