Olfactory tubercle circuits involved in odor valence assignment

项目摘要 感官刺激如何根据行为经验获得情感标签是至关重要的主题 在神经科学中的重要性，但一直很难研究，因为涉及复杂的大脑回路 这一过程。我认为嗅觉可能是询问这个问题的理想系统，因为 嗅球投射与腹侧基底节致密多巴胺能投射的直接接口 结构，嗅结节。此外，这种进化上保守的嗅觉来源 像嗅结节这样的边缘脑区的信息可能是提议的例外情况的基础 气味唤起积极或消极情绪反应的能力。我打算首先剖析一下 嗅结节回路在经典条件反射任务中的气味配价分配 显微内窥镜对单个D1型或D2型多巴胺受体进行钙活性成像 嗅结节内神经元的表达。然后我会消融嗅觉中的多巴胺终末 局部应用6-羟基多巴胺，并评估气味和预后的变化 在没有多巴胺输入的情况下，相同类型神经元的诱发活动。其次，我将开发一种 新的行为测试，以验证习得的气味联系导致气味的假设 与刺激-结果与刺激有关的偏好相比，偏好是唯一强烈的 另一种感觉形式(试听)。要做到这一点，我将首先识别类似的气味和声音刺激 然后在经典的条件反射任务中使用这些刺激。刺激后-结果 在训练中，小鼠对经典条件反射中使用的刺激的偏好将在 偏好测试。最后，我将测试嗅结节在气味结果学习和学习中的因果作用 在发展嗅觉偏好时使用双侧嗅结节病变。 总之，拟议的研究可能会大大有助于我们对(1) 加工潜在的价分配给感觉刺激，(2)功能回路机制 嗅结节，一个未被研究的大脑区域，以及(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.