CRCNS: Dynamical mechanisms of oscillation transitions in the olfactory system

CRCNS：嗅觉系统振荡转变的动力学机制

• 批准号: 8837265
• 负责人: Thomas A Cleland
• 金额: $ 33.1万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8837265
• 关键词: Action Potentials; Acute; Affect; Attention; Behavior; Behavioral; Biology; Biophysics; Brain region; Child; Cognitive; Collaborations; Complement; Complex; Computer Simulation; Coupled; Coupling; Data Set; Electrophysiology (science); Enrollment; Family; Female; Frequencies; Hodgkin Disease; Institution; Knowledge; Laboratories; Leadership; Mediating; Methods; Minority; Modeling; Mus; NCI Scholars Program; Neurons; Neurosciences; Odors; Olfactory tubercle; Output; Paper; Phase; Population; Process; Publications; Publishing; Rattus; Recruitment Activity; Research; Research Personnel; Research Technics; Rest; STEM field; Sampling; Science; Scientist; Sensory; Shapes; Slice; Structure; Students; Synapses; System; Time; Tissues; Training; Underrepresented Minority; Work; alertness; awake; base; flexibility; girls; information processing; network models; olfactory bulb; outreach program; piriform cortex; programs; relating to nervous system; respiratory; response

DESCRIPTION (provided by applicant): The emergence of coherent local field potentials (LFPs) in the beta (15-30 Hz) and gamma (35-100 Hz) frequency bands has been associated with attention, sensorimotor integration, and other active information processing states within and among brain regions. Beta/gamma coherence is broadly associated with action potential synchronization, which in turn has been hypothesized to define and delimit neural assemblies, and further to enable multiple assemblies of neurons within a population to synchronize within each assembly (but not among different assemblies) so that these multiple assemblies can compete to determine the systems output. The olfactory system has a strong and complex complement of LFP oscillations. Several different frequency bands are routinely observed, and are associated with particular behavioral tasks or states, such as acute sensory activity, resting alertness, and respiratory phases. Some oscillations coexist in the same structure; others appear to give way to one another. Some are local; others mediate interareal coupling either via LFP coherence or via subtler spike-field coherence in which periodic activity in the OB shapes the timing of action potentials in a limited assembly of neurons in a follower structure. Moreover, the olfactory system juxtaposes bottom-up network dynamics resulting from afferent stimulation with top-down dynamics arising from behavioral state factors, both affecting sensory information exported from olfactory bulb. Overall, the olfactory system is a particularly rich fied in which to study the biophysics and ethological utility of these neuronal dynamical systems in concert and within experimentally accessible tissues. This project will establish a robust, mechanistic, biophysically-based model of oscillations and synchronization in the mammalian olfactory system. The PIs will combine multichannel unit and LFP recordings from awake/behaving rats and from acute slices of the mouse OB using planar multielectrode array, and use the results to shape the expansion of an existing, biophysically detailed model of the early olfactory system. They will determine the extent to which the OB forms competing assemblies of gamma-coupled neurons and study beta oscillations as an interregional coupling mechanism with piriform cortex (PC) that supersedes these local gamma-coupled assemblies. Additional, less well-established OB interactions with olfactory tubercle and orbitofrontal cortex during odor sampling and response decisions also will be studied. Integrating these datasets into a common Hodgkin/Huxley-based network model will explicate the construction and utility of these systemwide dynamics based on their underlying cellular and network mechanisms. The proposed work takes a fairly well-characterized network and, via computational modeling, combines studies across different levels of analysis to build a mechanistic model of a complex dynamical system. The results will enable a deeper understanding of the dynamical flexibility of cortical circuits at many levels of analysis. Behavior provides tight control over oscillatory staes and cognitive processes associated with them, enabling explication of intact functional circuits. Slice electrophysiology and computational modeling will provide greater detail on the mechanistic, synaptic, neuromodulatory, and dynamical principles involved in generating and switching among these multiple states. The collaboration will benefit students at both institutions by integrating them into an interdisciplinary framework encompassing computational and experimental approaches, exposing students from diverse backgrounds to new research techniques and interdisciplinary and computational approaches to neuroscience. Close collaboration of the two investigators will transfer knowledge and methods across laboratories. Both laboratories actively train undergraduates in research and include them on many publications, and both laboratories actively recruit and train female and minority scientists in STEM fields. PI Kay has initiated participation in Project Exploration, an outreach program that provides access to science and scientists to underrepresented minority children and girls, and PI Cleland participates in the Leadership Alliance and Cornell Biology Scholars program for underrepresented minority and first-in-family students, and has published papers with undergraduate coauthors enrolled in these programs.

描述（由申请人提供）：β（15-30 Hz）和伽马（35-100 Hz）频带中相干局部场电位（LFP）的出现与大脑区域内和大脑区域之间的注意力、感觉运动整合和其他主动信息处理状态相关。 Beta/gamma 相干性与动作电位同步广泛相关，而动作电位同步又被假设为定义和界定神经组件，并进一步使群体内的多个神经元组件能够在每个组件内（但不在不同组件之间）同步，以便这些多个组件可以竞争确定系统输出。嗅觉系统有一个强大而复杂的 LFP 振荡补充。人们经常观察到几个不同的频段，这些频段与特定的行为任务或状态相关，例如急性感觉活动、静息警觉性和呼吸阶段。一些振荡同时存在于同一结构中；其他人似乎互相让路。有些是本地的；其他人通过 LFP 相干性或通过更微妙的尖峰场相干性介导区域间耦合，其中 OB 中的周期性活动塑造跟随结构中有限的神经元集合中动作电位的时序。此外，嗅觉系统将传入刺激产生的自下而上的网络动态与行为状态因素产生的自上而下的动态并置，两者都会影响从嗅球输出的感觉信息。总体而言，嗅觉系统是一个特别丰富的领域，可以在实验可及的组织内协同研究这些神经元动力系统的生物物理学和行为学效用。该项目将在哺乳动物嗅觉系统中建立一个稳健的、机械的、基于生物物理的振荡和同步模型。 PI 将使用平面多电极阵列将来自清醒/行为大鼠和小鼠 OB 急性切片的多通道单元和 LFP 记录结合起来，并利用结果来扩展现有的、生物物理详细的早期嗅觉系统模型。他们将确定 OB 形成伽马耦合神经元竞争性组件的程度，并研究 β 振荡作为与梨状皮层 (PC) 的区域间耦合机制，以取代这些局部伽马耦合神经元。另外，在气味采样和响应决策过程中，OB 与嗅结节和眶额皮层的不太确定的相互作用也将被研究。将这些数据集集成到基于霍奇金/赫胥黎的通用网络模型中，将根据其底层细胞和网络机制阐明这些全系统动态的构建和效用。拟议的工作采用了一个相当明确的网络，并通过计算建模，结合了不同分析层次的研究，建立了复杂动力系统的机械模型。这些结果将使人们能够在多个分析层面上更深入地了解皮层回路的动态灵活性。行为提供了对振荡状态和与之相关的认知过程的严格控制，从而能够解释完整的功能回路。切片电生理学和计算建模将提供有关这些多种状态的生成和切换所涉及的机械、突触、神经调节和动力学原理的更多细节。此次合作将使两个机构的学生受益，将他们整合到一个包含计算和实验方法的跨学科框架中，让来自不同背景的学生接触新的研究技术以及神经科学的跨学科和计算方法。两位研究人员的密切合作将在实验室之间转移知识和方法。两个实验室都积极培训本科生进行研究，并将他们纳入许多出版物中，并且两个实验室都积极招募和培训 STEM 领域的女性和少数族裔科学家。 PI Kay 已发起参与 Project Exploration，这是一项外展计划，为代表性不足的少数族裔儿童和女孩提供接触科学和科学家的机会，PI Cleland 参加了针对代表性不足的少数族裔和第一家庭学生的领导力联盟和康奈尔生物学学者计划，并与参加这些计划的本科生合著者发表了论文。