Experience-dependent modulation of innate neural circuits

 描述（由申请人提供）：大脑将外部世界的内部表征转化为适当的先天和适应性行为。阐明感觉信息如何通过层级系统传播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层和情感结构的通路相对较浅。此外，学习的嗅觉行为被认为可以改变先天反应，这表明这两种途径是交叉的。因此，确定的路径可以作为经验的基础，以塑造动物如何应对不可预测的世界。我们已经开发了遗传策略，证明了将信息从嗅球传递到杏仁皮质的刻板神经回路是先天厌恶和食欲行为所必需的。此外，我们还利用活性依赖基因arc的启动子来表达杏仁核皮层神经元中的光敏离子通道channelrhodopsin，该通道被气味激活，从而引发先天行为。这些神经元的光学激活导致适当的行为，重演了对先天气味的反应。因此，我们已经发现，杏仁核皮质神经元是必要的，并足以引起先天嗅觉驱动的行为反应。这个提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，皮质杏仁核是一个基板的先天途径。此外，梨状皮质，一个与嗅觉学习有关的结构，对皮质杏仁核有很强的投射。我们提出了一个模型，即从梨状皮质和直接延髓输入皮质杏仁核的处理联想输入的收敛提供了一个电路的经验依赖性嗅觉行为。我们将结合行为实验、分子遗传学和神经元活动的内窥镜成像来提出三个主要问题：1）皮质杏仁核是如何组织的，以引起不同的行为？2)从梨状皮质到皮质杏仁核的通路是先天行为的经验依赖性调节所必需的吗？3)从梨状皮质到皮质杏仁核的多突触回路是否在对新气味的适应性反应中起作用？在哥伦比亚大学的Richard阿克塞尔博士的主要指导下，该培训计划提供了一个全面的战略，用于在示范和协作的神经科学环境中获得必要的实验和专业技能。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，包括神经活动的体内成像和神经回路的映射。有针对性的导师指导，以及频繁的数据展示，将为我提供向独立过渡所必需的沟通和领导技能。从长远来看，这种支持将使我能够领导一个实验室，将分子和系统方法结合起来，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.