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示形式转化为适当的行为。阐明如何通过层次系统传播感官信息是迈向的重要一步了解大脑如何指导行为。嗅觉是一种可拖动的模型，因为路径从鼻子到杏仁核中的相关皮层和情感结构相对简洁。先天行为是动物之间刻板印象的，可能是由于遗传确定和保守而导致的电路，使其成为可拖动的模型。我们过去的工作揭示了皮质杏仁核（PLCOA）的电路介导了先天的吸引力和对气味的厌恶。了解感官器官如何连接到大脑产生不同价值的行为是一个重要的生物学问题，可以洞悉对感觉刺激的情感反应。我们已经将解剖学跟踪与功能相结合操纵以揭示PLCOA的两个输出，伏隔核（NAC）和内侧杏仁核（MEA），，能够分别引起方法和回避响应。此外，我们还有证据暗示PLCOA电路有一个地形组织。因此，我们假设PLCOA 包含地形有组织的标记线，以赋予气味诱发行为的价。该提案的目的是破译PLCOA电路及其与NAC和MEA的连接。我们已经证明了对NAC和MEA的皮质杏仁核预测能够生成方法，并且回避行为。此外，这些投射神经元似乎彼此不同。我们提出了一个 PLCOA将投影发送到NAC以发出正价，并向内侧杏仁核发出预测的模型信号避免。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回答三个基本问题：1）PLCOA预测 NAC和MEA介导了气味诱发的行为？ 2）PLCOA投影神经元如何解剖有组织？ 3）这些投影神经元及其下游靶标是否表现出对价的气味调节？这这些问题的答案将填补有关先天途径中气味代表的知识障碍和将此途径扩展到大脑延伸到行为输出。