The architecture and development of a sensory processing circuit for smell

气味感觉处理电路的架构和开发

基本信息

批准号：
8678898
负责人：
Kristin Kay Baldwin
金额：
$ 47.38万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-01 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8678898
关键词：
Afferent Neurons Amygdaloid structure Anatomy Animals Architecture Autistic Disorder Axon Behavior Behavioral Bioinformatics Biological Assay Biological Models Brain Brain region Characteristics Cognition Color Cues Defect Dendrites Detection Development Dimensions Disease Distant Electrophysiology (science)Exhibits Eye Failure Fright Future Generations Genes Genetic Genetic Programming Goals Hearing Human Individual Instinct Label Light Link Maintenance Maps Methods Mus Mutation Neurodegenerative Disorders Neurons Odors Olfactory Cortex Olfactory Learning Olfactory tubercle Output Play Process Property Proteins Resolution Role Schizophrenia Sensory Sensory Process Sister Site Smell Perception Stereotyping Synapses System Techniques Testing Tetanus Toxin Touch sensation Vibrissae Viral Vision base developmental genetics experience learned behavior nervous system disorder neural circuit neuropsychiatry novel olfactory bulb reconstruction relating to nervous system response stereotypy tool

项目摘要

DESCRIPTION (provided by applicant): Human cognition and behavior depend on the proper assembly and maintenance of neural circuits and genes that imperil these processes are increasingly linked to autism, schizophrenia and other neurological disorders. Neural activity and genetic programs contribute to different aspects of neural circuit development and architecture. In some sensory circuits, such as vision, hearing and touch, neurons with related response properties are organized in a stereotypic manner to form "maps" of sensory information. In these systems, genes and neural activity play complementary roles in forming and maintaining these maps. Less is known about the developmental principles that help to establish finer scale neural connectivity, particularly in processing regions that lack obvious spatial maps. Here, we propose to examine the impact of neural activity on circuits involved in the sense of smell. In particular, we will study the circuits formed by the mitral and tufted (MT) neurons, which receive inputs from defined groups of sensory neurons and transmit this information to multiple functionally distinct cortical processing centers responsible for olfactory learning and innate behaviors such as attraction or fear. MT neurons are important to study for two reasons. First, we have developed new viral tracing and neuron reconstruction techniques to label sets of "sister" MT neurons that respond to the same odors in the same animal and map their projections in three dimensions. This affords us a sensitive method to investigate fine scale wiring mechanisms. Second, individual MT neurons innervate multiple cortical targets, which each seems to posses a characteristic architecture. This allows us to simultaneously assess the impact of activity on multiple circuit architectures that are formed by different branches of the same MT axon. The central hypothesis of this proposal is that activity in MT neurons differentially regulates distinct aspects of olfactory circuit architecture. To test this hypothesi we propose three specific aims. First, we will determine whether projections of "sister" mitral and tufted (MT) neurons are stereotyped in cortical processing centers involved in innate behaviors. Second, we will synaptically silence olfactory sensory neurons and identify the features of olfactory bulb and cortical circuits that depend on sensory input. Third, we will synaptically silence MT neurons and identify aspects of local and cortical circuit architecture that depend on MT activity. Results of these studies will identify unknown activity-dependent mechanisms of olfactory neural circuit formation and predict which features of circuit architecture are likely tobe controlled by genetic programs. Defining these circuits with high resolution will facilitate future studies to identify genes implicated in building specific neural circuits and to assess the functional consequence of mutations linked to human neurodevelopmental or neurodegenerative diseases.

描述（由申请人提供）：人类认知和行为取决于神经回路的正确组装和维护，而危及这些过程的基因越来越多地与自闭症、精神分裂症和其他神经系统疾病联系在一起。神经活动和遗传程序有助于神经回路发育和结构的不同方面。在一些感觉回路中，例如视觉、听觉和触觉，具有相关反应特性的神经元以刻板的方式组织起来，形成感觉信息的“地图”。在这些系统中，基因和神经活动在形成和维护这些图谱方面发挥着互补作用。人们对有助于建立更精细尺度神经连接的发育原理知之甚少，特别是在缺乏明显空间图的处理区域。在这里，我们建议检查神经活动对涉及嗅觉的回路的影响。特别是，我们将研究由二尖瓣和簇状（MT）神经元形成的回路，这些神经元接收来自定义的感觉神经元组的输入，并将这些信息传输到多个功能不同的负责嗅觉的皮层处理中心学习和固有行为，例如吸引力或恐惧。 MT 神经元的研究很重要，原因有两个。首先，我们开发了新的病毒追踪和神经元重建技术，以标记对同一动物中相同气味做出反应的“姐妹”MT 神经元组，并在三个维度上绘制它们的投影。这为我们提供了一种研究精细尺度的灵敏方法接线机制。其次，单个 MT 神经元支配多个皮质目标，每个目标似乎都具有独特的结构。这使我们能够同时评估活动对同一 MT 轴突的不同分支形成的多个电路架构的影响。该提议的中心假设是 MT 神经元的活动差异性地调节嗅觉回路结构的不同方面。为了检验这个假设，我们提出了三个具体目标。首先，我们将确定“姐妹”二尖瓣和簇状（MT）神经元的投射是否在涉及先天行为的皮质处理中心中被定型。其次，我们将突触抑制嗅觉感觉神经元，并识别依赖于感觉输入的嗅球和皮质回路的特征。第三，我们将突触抑制 MT 神经元，并识别依赖于 MT 活动的局部和皮质回路架构的各个方面。这些研究的结果将确定嗅觉神经回路形成的未知活动依赖性机制，并预测回路结构的哪些特征可能由遗传程序控制。以高分辨率定义这些电路将有助于未来研究旨在识别与构建特定神经回路有关的基因，并评估与人类神经发育或神经退行性疾病相关的突变的功能后果。