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Deciphering the neural circuits that mediate innate olfactory behaviors.

破译介导先天嗅觉行为的神经回路。

基本信息

批准号：
10624337
负责人：
Cory Matthew Root
金额：
$ 39.5万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-15 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10624337
关键词：
Address Amygdaloid structure Anatomy Animals Anterior Appetitive Behavior Automobile Driving Behavior Behavioral Biological Brain Brain region Calcium Code Data Desire for food Disease Emotional Endoscopy Esthesia Exhibits Genetic Goals Higher Order Chromatin Structure Instinct Knowledge Label Lateral Measures Medial Mediating Modeling Motor output Mus Neurobiology Neurons Neurosciences Nose Nucleus Accumbens Odors Olfactory Pathways Optics Output Pathway interactions Perception Play Population Positive Valence Role Sense Organs Sensory Series Signal Transduction Smell Perception Stereotyping Stimulus Structure System Testing Translating Viral Volatilization Work anatomical tracing approach behavior avoidance behavior experimental study gain of function imaging approach insight loss of function microendoscopy nervous system disorder neural circuit olfactory bulb optogenetics organizational structure piriform cortex response sensory system tool two-photon

项目摘要

Project Summary The brain translates internal representations of the external world into appropriate 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 concise. Innate behaviors are stereotypical between animals and likely result from genetically determined and conserved circuits, making them a tractable model. Our past work has revealed circuits in the cortical amygdala (plCoA) that mediate innate attraction and aversion to odor. Understanding how the sense organ is wired to the brain to produce behaviors of different valence is an important biological problem and may provide insight into emotional responses to sensory stimulation. We have combined anatomical tracing with functional manipulations to reveal two outputs of the plCoA, the nucleus accumbens (NAc) and medial amygdala (MeA), that are capable of eliciting approach and avoidance responses, respectively. Further, we have evidence to suggest that there is a topographic organization to the plCoA circuitry. Thus, we hypothesize that the plCoA contains topographically organized labeled lines to impart valence on odor-evoked behaviors. The goal of this proposal is decipher the plCoA circuitry and its connections to the NAc and MeA. We have demonstrated that the cortical amygdala projections to NAc and MeA are able to generate approach and avoidance behaviors. Moreover, these projection neurons appear to be distinct from each other. We propose a model whereby the plCoA sends projections to the NAc to signal positive valence, and to medial amygdala to signal aversion. We will employ a combination of behavioral experiments, viral tracing, genetics and endoscopic imaging of neuronal activity to answer three fundamental questions: 1) Do the plCoA projections to NAc and MeA mediate odor-evoked behaviors? 2) How are the plCoA projection neurons anatomically organized? 3) Do these projection neurons and their downstream targets exhibit odor tuning for valence? The answers to these questions will fill a knowledge gab about the representation of odor in the innate pathway and extend this pathway deeper into the brain towards behavioral output.

项目摘要大脑将外部世界的内部表征转化为适当的行为。阐明感官信息如何通过等级系统传播是迈向了解大脑如何指导行为。嗅觉是一个易于处理的模型，因为从鼻子到杏仁核中的关联皮层和情感结构相对简洁。先天动物之间的行为是刻板的，可能是由遗传决定和保守的电路，使它们成为一个易于处理的模型。我们过去的工作揭示了大脑皮层杏仁核（plCoA）中的回路介导对气味的天生吸引和厌恶。了解感觉器官如何连接到大脑，不同价态的产生行为是一个重要的生物学问题，对感官刺激的情绪反应我们将解剖追踪与功能追踪相结合，操作以揭示p1CoA的两个输出，丘脑核（NAc）和内侧杏仁核（MeA），能够分别引起接近和回避反应。此外，我们有证据表明，表明plCoA回路存在地形组织。因此，我们假设plCoA 包含地形组织的标记线，以赋予气味诱发行为的效价。该提案的目标是破译plCoA电路及其与NAc和MeA的连接。我们已经证明，杏仁核皮质投射到NAc和MeA能够产生方法，回避行为。此外，这些投射神经元似乎彼此不同。我们提出了一个模型，其中plCoA将投射发送到NAc以发出阳性价信号，并发送到内侧杏仁核以信号厌恶我们将采用行为实验，病毒追踪，遗传学和神经元活动的内窥镜成像以回答三个基本问题：1）将plCoA投射到 NAc和MeA介导气味诱发行为？2)plCoA投射神经元在解剖学上组织？3)这些投射神经元和它们的下游靶细胞是否表现出对化合价的气味调谐？的这些问题的答案将填补关于气味在先天途径中的表现的知识空白，将这条通路延伸到大脑更深处，以实现行为输出。