The synaptic basis of cortical taste processing

皮质味觉处理的突触基础

• 批准号: 8492060
• 负责人: Alfredo Fontanini
• 金额: $ 31.17万
• 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/8492060
• 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.

描述（由申请人提供）：味觉皮层（GC）中的神经元对其发射率的时变调制对感觉刺激做出反应。麻醉和清醒动物的电生理记录表明，刺激呈现发作后的点火活性可能会在几秒钟内变化（Grossman等，2008; Gutierrez等，2010; Jones等，2007; Stapleton et al。; Stapleton et al。，2006; 2006; Yamamoto et al。这些动力学是味觉反应的关键特征，据信可以介导味觉信息的不同方面的处理（Fontanini和Katz，2006，2009; Gutierrez等，2010; Katz等，2002a）。尽管大量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在更长的延迟（即数百毫秒）中表现出快速的味道反应，而有些则被激活，而另一些则根本没有反应。依靠GABA阻滞剂双瓜氨酸点局部输注的药理实验将抑制作用作为塑造反应的关键参与者（Ogawa等，1998）。但是，缺乏细胞外技术的突触分辨率限制了我们对抑制与激发之间相互作用如何影响不同神经元反应的时间过程的理解。 该提案中的实验旨在检验一般假设，即随时间变化的尖峰反应是由激发和抑制的特定组合确定的。体内细胞内技术的使用将允许解决麻醉大鼠激发和抑制之间平衡的突触电位（Haider等，2006; Stone等，2011; Wilent and Contreras，2005）。细胞内注射生物细胞，然后进行组织学重建，用于鉴定细胞类型和神经元的位置 记录。鉴定记录的神经元的能力将有助于理解GC不同层和分裂（颗粒状，不足和农业）中的细胞是否显示出突触相互作用的特定模式。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素如何将自下而上的感觉输入与自上而下的调制进行整合。该框架代表了在完整动物中研究GC的完全新颖的方法，并提供了良好基础的首次集成式壳质处理。