Experience-dependent modulation of innate neural circuits

先天神经回路的经验依赖性调节

• 批准号: 9012812
• 负责人: Cory Matthew Root
• 金额: $ 17.56万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9012812
• 关键词: Adaptive Behaviors; Address; Affect; Amygdaloid structure; Anatomy; Animals; Anterior; Appetitive Behavior; Area; Association Learning; Behavior; Behavioral; Brain; Calcium; Choice Behavior; Communication; Cues; Data; Disease; Elements; Emotional; Environment; Evolution; Future; Genes; Genetic; Goals; Health; Image; Instinct; Ion Channel; Laboratories; Lead; Leadership; Learning; Link; Maps; Mediating; Mentors; Mentorship; Modeling; Molecular; Molecular Genetics; Mus; Neurobiology; Neurons; Neurosciences; Nose; Odors; Olfactory Cortex; Olfactory Learning; Optics; Output; Pathway interactions; Perception; Play; Predictive Value; Process; Role; Sensory; Series; Shapes; Smell Perception; Stereotyping; Structure; Synapses; System; Training; Translating; Universities; Work; behavioral response; experience; flexibility; in vivo imaging; insight; learned behavior; nervous system disorder; neural circuit; novel; olfactory bulb; optogenetics; piriform cortex; promoter; relating to nervous system; research study; response; sensory system; skills; success; tool; transmission process

 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.

 描述（由适用提供）：大脑将外部世界的内部表示转化为适当的先天和适应性行为。阐明如何通过分层系统传播感官信息是了解大脑如何指导行为的重要一步。嗅觉是一种可进行的模型，因为从鼻子到关联皮层的途径和杏仁核中的情绪结构相对较浅。此外，被学到的嗅觉行为被认为可以改变先天反应，这表明这两种途径相交。因此，确定的途径可以用作底物，经验可以塑造动物对一个不可预测的世界的反应。我们已经开发了遗传策略，这些遗传策略表明，对嗅觉鳞茎传输信息形成的刻板神经回路是天生的厌恶和食用性行为所必需的。此外，我们还为活动依赖性基因ARC的启动子发表了光敏感的离子通道ChannelRhopopsin，在由引起先天行为的气味激活的皮质杏仁核神经元中。这些神经元的光学激活导致适当的行为，概括了对先天气味的反应。这就是我们透露，皮质杏仁核中的神经元既需要且足以引起先天嗅觉驱动的行为反应。该建议的目的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。我们已经证明了皮质杏仁核是天生途径的底物。此外，在嗅觉学习中实现的梨状皮层对皮质杏仁核有很大的投影。我们提出了一个模型，通过该模型，从梨状皮层和直接的灯泡输入到皮质杏仁核的处理的关联输入的收敛性为经验依赖的嗅觉行为提供了电路。我们将采用行为实验，分子遗传学和神经元活性的内窥镜成像的结合来提出三个主要问题：1）如何组织皮质杏仁核以引起不同的行为？ 2）从梨状皮层到与先天行为的经验依赖性调节所需的皮质杏仁核的途径？ 3）从梨状皮层到皮质杏仁核的多突触电路在适应性反应中起作用吗？在哥伦比亚大学理查德·阿克塞尔（Richard Axel）的主要心态下，培训计划为在典范和协作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策略。经验丰富的合作者团队将提供有关我短期和长期成功至关重要的技能培训，包括神经元活动的体内成像和神经元电路的映射。专注的心理指导以及经常数据展示将为我过渡到独立至关重要的沟通和领导能力。从长远来看，这种支持将使我领导一个合并分子和系统方法的实验室，以探索内部状态和过去的经验如何影响选择行为。