Synaptic Processes Mediating Cortical Odor Coding

介导皮质气味编码的突触过程

基本信息

批准号：
8708819
负责人：
Kevin Franks
金额：
$ 24.29万
依托单位：
DUKE UNIVERSITY
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：
2012-09-01 至 2016-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8708819
关键词：
Address Award Brain Cell Fraction Cells Chemicals Code Complement Computer Simulation Coupled Data Dependovirus Elements Event Feedback Fire - disasters Future Image In Vitro Individual Instruction Intuition Laboratories Lead Ligands Light Measures Mediating Mentors Methods Microscopy Modeling Mus Neurobiology Neurons Odorant Receptors Odors Olfactory Pathways Output Pattern Phase Play Population Probability Process Property Pyramidal Cells Recruitment Activity Recurrence Reporting Research Role Shapes Simulate Solutions Specificity Synapses Testing Tetanus Toxin Toxin Translating Universities Visit Whole-Cell Recordings Work abstracting design feeding in vivo in vivo imaging interest neural circuit olfactory bulb optical imaging optogenetics piriform cortex programs receptor research study response selective expression two-photon virus genetics

项目摘要

PROJECT SUMMARY (See instructions); Abstract Olfactory information is encoded by combinations of olfactory bulb glomeruli, which individually represent distinct chemical features of different odorants. This information is transmitted to the piriform cortex, where it drives activation of ensembles of neurons whose concerted activity is thought to lead to a holistic odor percept. Piriform neurons are also interconnected by a rich recurrent circuitry. Here, we propose to extend our previous work dissecting the cellular mechanisms that shape these corticalensembles. We are particularly interested in the problem of concentration invariance. Odorant receptor specificity depends on ligand concentration, with more receptors being activated at higher odorant concentrations. However, odors retain their identity over a large range of concentrations, requiring that odor representations be normalized with respect to concentration somewhere along the olfactory pathway. Such normalization occurs in neural circuits throughout the brain, although the cellular mechanisms underlying this normalization remain poorly understood. Recent experiments suggest odor-evoked activity in piriform cortex is relatively concentration invariant, consistent with the relatively concentration-invariant quality of the odor percept. In the mentored phase of this award we examined the recurrent piriform network in vitro and discovered features of this circuit that are poised to play a major role in shaping odor-evoked cortical activity and suggest a circuit-level solution to effecting concentration invariance. Here, we will quantitatively characterize the transformation of odor representations from olfactory bulb to piriform cortex using in vivo two-photon microscopy to image odor-evoked activity in populations of olfactory bulb mitral cells and principal neurons in piriform cortex (Aim 1). We will build an experimentally constrained, network-level computational model to test the sufficiency of our circuit-level model for effecting concentration invariance (Aim 2). Finally, we will use genetic and viral strategies to selectively eliminate the recurrent circuitry to directly test the role of these circuits in mediating concentration invariance (Aim 3). This research program employs a rich arsenal of conceptual and technical approaches that have

项目摘要（参见说明）；摘要嗅觉信息是由嗅球肾小球的组合编码的，嗅球肾小球分别代表不同气味的不同化学特征。这些信息被传输到梨状皮层，在那里它驱动神经元群的激活，这些神经元的协同活动被认为会导致整体的气味感知。梨状神经元也通过丰富的循环电路相互连接。在这里，我们建议扩展我们之前的工作，剖析塑造这些皮质群的细胞机制。我们对浓度不变性问题特别感兴趣。气味受体特异性取决于配体浓度，气味浓度越高，激活的受体越多。然而，气味在很大的浓度范围内保持其特性，要求气味表征相对于嗅觉路径上某处的浓度进行标准化。这种正常化发生在整个大脑的神经回路中，尽管这种正常化背后的细胞机制仍然知之甚少。最近的实验表明，梨状皮层中的气味诱发活动相对浓度不变，这与气味感知的相对浓度不变质量一致。在该奖项的指导阶段，我们在体外检查了循环梨状网络，发现了该电路的特征，这些特征将在塑造气味诱发的皮层活动中发挥重要作用，并提出了一种电路级解决方案来实现浓度不变性。在这里，我们将使用体内双光子显微镜定量表征从嗅球到梨状皮层的气味表征的转变，以对嗅球二尖瓣细胞群和梨状皮层主要神经元中气味诱发的活动进行成像（目标 1）。我们将建立一个实验约束的网络级计算模型来测试我们的电路级模型对于实现浓度不变性的充分性（目标 2）。最后，我们将使用遗传和病毒策略选择性地消除循环回路，以直接测试这些回路在介导浓度不变性中的作用（目标 3）。该研究计划采用了丰富的概念和技术方法，这些方法