The synaptic basis of cortical taste processing

皮质味觉处理的突触基础

• 批准号: 8340794
• 负责人: Alfredo Fontanini
• 金额: $ 30.74万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 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/8340794
• 关键词: Address; Animals; Area; Attention; Bicuculline; Cell Nucleus; Cells; Citric Acid; Code; Electric Stimulation; Equilibrium; Frequencies; Heterogeneity; Indium; Infusion procedures; Injection of therapeutic agent; Location; Measures; Mediating; Membrane Potentials; Neurons; Optics; Palate; Pathway interactions; Pattern; Physiologic pulse; Process; Property; Protocols documentation; Quinine; Rattus; Relative (related person); Research; Resolution; Role; Sensory; Shapes; Sodium Chloride; Sodium Glutamate; Stimulus; Sucrose; Synapses; Synaptic Potentials; Taste Perception; Techniques; Testing; Thalamic structure; Time; Tongue; Training; Water; Work; awake; base; biocytin; cell type; design; extracellular; gamma-Aminobutyric Acid; in vivo; insight; millisecond; novel; novel strategies; optogenetics; postsynaptic; reconstruction; relating to nervous system; research study; response; sensory stimulus

DESCRIPTION (provided by applicant): Neurons in the gustatory cortex (GC) respond to sensory stimuli with time-varying modulations of their firing rates. Electrophysiological recordings from anesthetized and awake animals have shown that firing activity can change over few seconds following the onset of stimulus presentation (Grossman et al., 2008; Gutierrez et al., 2010; Jones et al., 2007; Stapleton et al., 2006; Yamamoto et al., 1984b; Yokota et al., 2011). These dynamics are a critical feature of gustatory responses and are believed to mediate the processing of different aspects of gustatory information (Fontanini and Katz, 2006, 2009; Gutierrez et al., 2010; Katz et al., 2002a). While a great deal of work has focused on understanding the functional significance of these patterns, little is known about their genesis. I is not known, for instance, why some neurons display rapid taste responses, some are activated at much longer latencies (i.e. hundreds of milliseconds) and some others do not respond at all. Pharmacological experiments relying on local infusions of the GABA blocker bicuculline point to inhibition as a key player in shaping responses (Ogawa et al., 1998). However, the lack of synaptic resolution of extracellular techniques has limited our understanding of how interactions between inhibition and excitation could influence the time course of responses in different neurons. The experiments in this proposal are designed to test the general hypothesis that time-varying spiking responses are determined by specific combinations of excitation and inhibition. The use of in vivo intracellular techniques will allow to resolve synaptic potentials ad dissect the balance between excitation and inhibition in anesthetized rats (Haider et al., 2006; Stone et al., 2011; Wilent and Contreras, 2005). Intracellular injection of biocytin, followed by histological reconstructions, will be used to identify the cell type and the location of the neuron recorded. The ability to identify the recorded neurons will be instrumental in understanding whether cells in the different layers and divisions (granular, dysgranular and agranular) of GC show specific patterns of synaptic interactions. The analysis of synaptic responses to thalamic, amygdalar and gustatory stimulation will allow us to determine how specific elements in the circuit integrate bottom-up sensory inputs with top-down modulations This framework represents an entirely novel approach to the study of GC in intact animals and promises to provide the first integrative view of the synaptic bases of gustatory cortical processing. PUBLIC HEALTH RELEVANCE: This proposal aims at understanding the synaptic basis of taste processing in the gustatory cortex. The experiments are designed to unveil how the integration of excitatory and inhibitory potentials shapes neural responses to gustatory stimuli in different subpopulations of cortical neurons. The contribution of two pathways, the thalamic and the amygdalar pathway, will be investigated. The combination of in vivo intracellular techniques, electrical stimulation, optogenetic approaches and sensory stimulation will allow us unprecedented resolution in the study of this largely unexplored topic in taste research. The results of this effort will provide novel and important insights on the cortical mechanism underlying taste processing. Identifying the role of different neural subpopulation and the contribution of thalamic and amygdalar pathways will provide selective targets for manipulating the perception of taste quality and valence in normal and pathological conditions.

描述（由申请人提供）：味觉皮层（GC）中的神经元对感觉刺激的反应是其放电率的时变调制。来自麻醉和清醒动物的电生理学记录已经表明，在刺激呈现开始之后，放电活动可以在几秒钟内改变（Grossman等人，2008; Gutierrez等人，2010; Jones等人，2007;斯台普顿等人，2006; Yamamoto等人，1984 b; Yokota等人，2011年）。这些动力学是味觉反应的关键特征，并且被认为介导味觉信息的不同方面的处理（Fontanini和Katz，2006，2009; Gutierrez等人，2010; Katz等人，2002年a）。虽然大量的工作集中在理解这些模式的功能意义上，但对它们的起源知之甚少。例如，我不知道为什么有些神经元表现出快速的味觉反应，有些神经元在更长的潜伏期（即数百毫秒）被激活，而另一些神经元则根本没有反应。依赖于GABA阻断剂荷包牡丹碱的局部输注的药理学实验指出抑制是形成反应的关键因素（Ogawa等人，1998年）。然而，细胞外技术的突触分辨率的缺乏限制了我们对抑制和兴奋之间的相互作用如何影响不同神经元中反应的时间过程的理解。 本提案中的实验旨在测试以下一般假设：时变尖峰响应是由兴奋和抑制的特定组合决定的。体内细胞内技术的使用将允许解析突触电位并剖析麻醉大鼠中兴奋与抑制之间的平衡（Haider等人，2006; Stone等人，2011年; Wilent和Contreras，2005年）。细胞内注射生物胞素，然后进行组织学重建，将用于识别细胞类型和神经元的位置 记录下来。识别记录的神经元的能力将有助于理解GC的不同层和分区（颗粒，dysgranular和agranular）中的细胞是否显示出特定的突触相互作用模式。对丘脑、杏仁核和味觉刺激的突触反应的分析将使我们能够确定电路中的特定元件如何将自下而上的感觉输入与自上而下的调制相结合。该框架代表了完整动物中GC研究的一种全新方法，并有望提供味觉皮层处理的突触基础的第一个综合观点。 公共卫生相关性：该提案旨在了解味觉皮层中味觉处理的突触基础。这些实验旨在揭示兴奋性和抑制性电位的整合是如何塑造味觉刺激的神经反应的， 皮层神经元的不同亚群。两个途径的贡献，丘脑和杏仁核途径，将进行调查。体内细胞内技术，电刺激，光遗传学方法和感官刺激的结合将使我们在味觉研究中这个基本上未探索的主题的研究中获得前所未有的解决方案。 这项工作的结果将提供新的和重要的见解的皮层机制的味觉加工。确定不同的神经亚群的作用和丘脑和杏仁核通路的贡献将提供选择性的目标操纵的味觉质量和效价在正常和病理条件下的感知。