Experience-dependent modulation of innate neural circuits

 描述(由申请者提供)：大脑将外部世界的内部表征转化为适当的与生俱来的适应性行为。阐明感觉信息是如何通过分级系统传播的，是理解大脑如何指导行为的重要一步。嗅觉是一个易于处理的模型，因为从鼻子到杏仁核中的联合皮质和情绪结构的通路相对较浅。此外，习得的嗅觉行为被认为可以改变天生的反应，这表明这两条途径是相交的。因此，确定的路径可以作为一种底物，经验在其上作用于塑造动物如何对不可预测的世界做出反应。我们已经开发出遗传策略，证明从嗅球到杏仁皮质传递信息的刻板神经回路对于天生的厌恶和食欲行为是必要的。此外，我们利用活性依赖基因的启动子Arc，在杏仁皮质神经元中表达光敏离子通道，通道视紫红质，这种通道被气味激活，引发先天行为。这些神经元的光学激活导致适当的行为，概括了对天生气味的反应。因此，我们揭示了杏仁体皮质中的神经元是诱发先天嗅觉驱动的行为反应的必要条件和充分条件。这项建议的目标是进一步定义先天行为的途径，并确定通过经验调节行为的潜在机制。我们已经证明杏仁皮质是先天通路的底物。此外，梨状皮质，一种与嗅觉学习有关的结构，有很强的投射到皮质无节核。我们提出了一个模型，在这个模型中，来自梨状皮质的经过处理的联想输入和直接的延髓输入汇聚到杏仁皮质，为经验依赖的嗅觉行为提供了一个回路。我们将结合行为实验、分子遗传学和神经活动的内窥镜成像来提出三个主要问题：1)杏仁皮质是如何组织起来的，以引发不同的行为？2)从梨状皮质到杏仁皮质的通路是否需要对先天行为的经验依赖性调节？3)从梨状皮质到杏仁皮质的多突触回路是否在对新气味的适应性反应中发挥作用？该培训计划在哥伦比亚大学理查德·阿克塞尔博士的主要指导下，为在模范和协作的神经科学环境中获得必要的实验和专业技能提供了全面的战略。一个经验丰富的合作者团队将提供对我的短期和长期成功至关重要的技能培训，包括神经活动的活体成像和神经回路的映射。有重点的导师指导，加上频繁的数据展示，将提供对我向独立过渡至关重要的沟通和领导技能。从长远来看，这种支持将使我有能力领导一个融合了分子和系统方法的实验室，探索内部状态和过去的经验如何影响选择行为。

 DESCRIPTION (provided by applicant): The brain translates internal representations of the external world into appropriate innate and adaptive behaviors. Elucidation of how sensory information is propagated through hierarchical systems is an important step towards understanding how the brain instructs behavior. The sense of smell is a tractable model because the pathways from the nose to associational cortex and emotional structures in the amygdala are relatively shallow. Moreover, Learned olfactory behaviors are thought to modify innate responses, suggesting that the two pathways intersect. Thus, determined pathways may serve as a substrate upon which experience acts to shape how animals respond to an unpredictable world. We have developed genetic strategies that demonstrate that a stereotyped neural circuit that transmits information form the olfactory bulb to the cortical amygdala is necessary for innate aversive and appetitive behaviors. Moreover, we have employed the promoter of the activity-dependent gene, arc, to express the photosensitive ion channel, channelrhodopsin, in neurons of the cortical amygdala activated by odors that elicit innate behaviors. Optical activation of these neurons leads to appropriate behaviors that recapitulate the responses to innate odors. Thus, we have revealed that neurons in the cortical amygdala are both necessary and sufficient to elicit innate olfactory-driven behavioral responses. The goal of this proposal is to further define pathways for innate behaviors and identify the underlying mechanisms for modulation of behavior by experience. We have demonstrated that the cortical amygdala is a substrate for innate pathways. Moreover, piriform cortex, a structure implicated in olfactory learning, has a strong projection to cortical amgydala. We propose a model whereby the convergence of processed associational input from piriform cortex and direct bulbar input to cortical amygdala provides a circuit for experience-dependent olfactory behaviors. We will employ a combination of behavioral experiments, molecular genetics and endoscopic imaging of neuronal activity to ask three principal questions: 1) How is the cortical amygdala organized to elicit different behaviors? 2) Is the pathway from piriform cortex to the cortical amygdala required for experience-dependent modulation of innate behaviors? 3) Does the polysynaptic circuit from piriform cortex to cortical amygdala play a role in adaptive responses to novel odors? The training plan, under the primary mentorship of Dr. Richard Axel at Columbia University, provides a comprehensive strategy for acquiring the necessary experimental and professional skills within an exemplary and collaborative neuroscience environment. An experienced team of collaborators will provide training in skills critical for my short- and long-term success, including in vivo imaging of neural activity and mapping of neural circuits. Focused mentor guidance, alongside frequent data presentation, will provide the communication and leadership skills vital for my transition to independence. In the long-term, this support will equip me to lead a laboratory that merges molecular and systems approaches to explore how internal states and past experiences affect choice behaviors.