Vagal Influence on Brainstem Plasticity and Neural Coding of Taste

迷走神经对脑干可塑性和味觉神经编码的影响

• 批准号: 8891094
• 负责人: Krzysztof Czaja
• 金额: $ 63.37万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8891094
• 关键词: Advanced Development; Affect; Animals; Axotomy; Behavioral; Body Weight decreased; Brain; Brain Stem; Cells; Code; Communication; Complex; Consumption; Cream; Data; Decision Making; Development; Diet; Eating; Electrophysiology (science); Ensure; Flavoring; Food; Frequencies; Gastric Bypass; Glutamates; Goals; Health; Hormonal Change; Human; Inflammatory Response; Intake; Knowledge; Link; Methods; Neuronal Plasticity; Neurons; Nucleus solitarius; Obesity; Operative Surgical Procedures; Patients; Plastics; Prevalence; Process; Public Health; Rattus; Reporting; Research; Risk; Role; Signal Transduction; Stimulus; Stomach; Synapses; Synaptic plasticity; Taste Perception; Taste preferences; Testing; Therapeutic Intervention; Tracer; United States; Vagotomy; Vagus nerve structure; Visceral Afferents; Withdrawal; Work; awake; bariatric surgery; base; common treatment; density; experience; feeding; gastrointestinal; innovation; nerve supply; neural circuit; neurochemistry; neuromechanism; neurophysiology; neurotransmission; novel; patch clamp; preference; public health relevance; relating to nervous system; research study; response; sweet taste perception; taste stimuli

 DESCRIPTION (provided by applicant): Roux-en-Y gastric bypass (RYGB) is the most effective method to achieve major, long-term weight loss. Patients who have undergone RYGB often report an aversion to calorie-dense foods. However, mechanisms underlying the effects of RYGB on taste alterations are incompletely understood. Our long-term goal is to understand the neural mechanisms that determine taste alterations following diet-induced obesity (DIO) and RYGB. Specifically, we want to detail the neuroanatomical, neurochemical and neurophysiological sequelae of reorganization of subdiaphragmatic vagal afferents, resulting from obesity and following RYGB, as they relate to gustatory signaling in nucleus of the solitary tract (NTS). Our central hypothesis is that damage to the gastric branches of the vagus, a consequence of RYGB, induces synaptic plasticity and circuit reorganization in the intermediate (feeding) and rostral (gustatory) NTS. Considering the NTS integrates both gustatory and gastrointestinal afferent information, we predict these changes in primary visceral afferent signaling fundamentally change how information about taste is encoded. Our central hypothesis will be tested by achieving the following specific aims: Specific Aim 1: Test the hypothesis that gastric vagotomy (VGX) and RYGB surgery induce reorganization and synaptic plasticity in the rostral NTS via transient withdrawal of central vagal afferent terminals from the caudal and intermediate NTS. Changes in vagal innervation will be investigated at the morphological and functional levels using a combination of anterograde tracers, synapse specific markers and patch-clamp electrophysiology in horizontal brain sections. We expect that, because of the known caudal-to-rostral projections within the NTS, the weakened vagal input experienced by DIO and further altered by RYGB will be reflected in subtle alterations in glutamate release and efficacy in the NTS. Specific Aim 2: Using electrophysiological recordings from the NTS of awake rats, we will test the hypothesis that obesity, gastric VGX and RYGB selectively modify taste-related intranuclear communication and that this effect will be reflected in the taste-evoked responses among NTS neurons. Analyses will focus on quantifying functional connections among ensembles of simultaneously recorded NTS cells as well as determining the information contributed by rate and temporal coding in taste-evoked responses. The proposed work is innovative because it connects the role of vagus nerve damage-induced plasticity within the NTS with taste alterations following DIO and RYGB. Results, of the proposed project, will provide a deeper understanding of the effects of obesity and RYGB on the neural circuitry underlying gustatory signaling in the brainstem. This knowledge will enable more systematic and targeted manipulations, aimed at revealing mechanisms by which RYGB reduces consumption of high-caloric foods and advance the development of novel surgical and non-surgical therapeutic interventions, to promote effective weight loss.

 描述（由适用提供）：roux-en-y胃旁路（RYGB）是实现重大长期体重减轻的最有效方法。对卡路里密集食品的厌恶患者。但是，尚不完全了解RYGB对味觉改变影响的机制。我们的长期目标是了解饮食引起的肥胖症（DIO）和RYGB后决定口味改变的神经机制。具体而言，我们希望详细介绍肥胖和rygb之后引起的亚脑dag骨迷走神经传入的重新组织的神经解剖学，神经化学和神经生理的后遗症，因为它们与固体核核核核（NTS）的核心（NTS）中的脾性相关。我们的中心假设是，RYGB的结果是对迷走神经的胃分支的损害，诱导了中间体（喂养）和隆特（Gustatoral）NTS的合成可塑性和回路重组。考虑到NTS整合了味觉和胃肠道传入信息，我们预测主要内脏传入信号的这些变化从根本上改变了对味觉的信息的编码方式。我们的中心假设将通过实现以下特定目的来检验：具体目的1：检验胃迷走术（VGX）和RYGB手术的假设，可通过暂时戒断中央迷幻的终端从Caudal和Intermendmendimed Nts中引起连续性NTS中的重组和突触可塑性。迷走神经支配的变化将在水平脑切片中的顺行示踪剂，突触特定标记和斑块钳电生理学的结合下在形态和功能水平上进行研究。我们预计，由于NTS内已知的尾尾延伸性投影，DIO经历的迷走型输入弱，而RYGB进一步改变将反映在谷氨酸释放的细微变化和NTS中的有效性中。具体目的2：使用来自清醒大鼠NTS的电生理记录，我们将测试以下假设：观察结果，胃VGX和RYGB选择性地修改与味觉相关的插图通信，并且这种效果将反映在味觉探测的中 NTS神经元之间的反应。分析将集中于量化简单记录的NTS单元的集合之间的功能连接，并确定通过味道引起的响应中的速率和临时编码贡献的信息。拟议的工作具有创新性，因为它连接了迷走神经损伤引起的NTS在DIO和RYGB之后的口味改变的作用。拟议项目的结果将更深入地了解肥胖和RYGB对脑干中阵风信号的神经元电路的影响。这些知识将实现更多的系统性和有针对性的操作，旨在揭示RYGB减少高热量食品的消费并推动新型外科手术和非手术治疗干预措施的发展，从而促进有效的体重减轻。