Cellular and synaptic mechanisms of cortical taste coding in awake-behaving mice

清醒小鼠皮质味觉编码的细胞和突触机制

• 批准号: 8546154
• 负责人: DUSTIN M GRAHAM
• 金额: $ 1.42万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-15 至 2013-12-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8546154
• 关键词: Action Potentials; Adult; Affect; Anesthesia procedures; Animals; Area; Automobile Driving; Blood Vessels; Calcium; Cells; Characteristics; Chemicals; Childhood; Chronic; Code; Data; Dendrites; Development; Diabetes Mellitus; Electrodes; Electrophysiology (science); Equilibrium; Food; Foundations; Future; Goals; Head; Image; Individual; Investigation; Lateral; Location; Maps; Measures; Methods; Modeling; Mus; Nature; Neurons; Non-Insulin-Dependent Diabetes Mellitus; Pattern; Play; Population; Preparation; Process; Property; Public Health; Public Policy; Rattus; Reliance; Research; Resolution; Role; Scheme; Shapes; Site; Solutions; Stimulus; Synapses; Synaptic Potentials; System; Taste Perception; Techniques; Testing; Time; Training; Work; awake; biocytin; career; extracellular; follow-up; in vivo; novel; nutrition; patch clamp; reconstruction; response; sensory stimulus; sweet taste perception

DESCRIPTION (provided by applicant): The exact nature and mechanism of encoding chemical stimuli in primary gustatory cortex is a matter of debate. Chronic extracellular recordings from awake-behaving rats suggest a dynamic and distributed code 4-10. This model emphasizes the unique spatio/temporal patterns of activity among groups of broadly tuned neurons acting as dynamic ensembles. However, recent data from anesthetized mice using in-vivo calcium imaging show a precise gustatopic map of primary tastes in the cortex 1. This suggests a coding scheme of sharply tuned gustatory cortical neurons arranged in topographically organized clusters. While the evidence for an organized cortical map representing primary tastes is intriguing, enthusiasm for such a map is tempered by the reliance on anesthetized animals 1-3. Anesthesia is well known to cause aberrant and artificial cortical network dynamics, significantly affecting processing of sensory stimuli 11. This proposal will resolve this problem by directly testing the general hypothesis that taste responsive neurons in gustatory cortex from awake-behaving mice are narrowly tuned and topographically organized. This will be accomplished by using a unique combination of in vivo extracellular and whole-cell patch-clamp electrophysiology, with a novel head-restrained mouse preparation that allows precise and systematic targeting of recordings throughout gustatory cortex in awake-behaving mice. The specific aims will study the functional organization of the gustatory cortex in awake-behaving animals with unprecedented detail, from the network-level to detailed synaptic mechanisms. Aim 1: Taste responses in gustatory cortex are narrowly tuned and functionally organized into topographic clusters in awake-behaving mice. Aim 2: Single-unit taste responses reflect mapped multi-unit activity. Aim 3: A balance of excitatory and inhibitory synaptic conductances drive taste responses in gustatory cortical neurons and shapes tuning.

描述（由申请人提供）：初级味觉皮层编码化学刺激的确切性质和机制是一个有争议的问题。清醒行为大鼠的慢性细胞外记录表明存在动态且分布式的代码 4-10。该模型强调了作为动态整体的广泛调整的神经元组之间独特的时空活动模式。然而，最近使用体内钙成像技术从麻醉小鼠获得的数据显示了大脑皮层 1 中主要味觉的精确味觉图。这表明了一种按地形组织的簇排列的敏锐味觉皮层神经元的编码方案。虽然代表主要口味的有组织的皮质地图的证据很有趣，但对麻醉动物的依赖削弱了人们对这种地图的热情 1-3。众所周知，麻醉会导致异常的人工皮质网络动力学，显着影响感觉刺激的处理11。该提案将通过直接测试一般假设来解决这个问题，即清醒行为小鼠的味觉皮层中的味觉反应神经元是狭窄调节和拓扑组织的。这将通过使用体内细胞外和全细胞膜片钳电生理学的独特组合以及新型头约束小鼠制剂来实现，该制剂允许精确和系统地针对清醒行为小鼠的整个味觉皮层进行记录。具体目标将以前所未有的细节研究清醒动物味觉皮层的功能组织，从网络层面到详细的突触机制。 目标 1：在清醒行为的小鼠中，味觉皮层的味觉反应被严格调节并在功能上组织成拓扑簇。 目标 2：单单元味觉反应反映映射的多单元活动。 目标 3：兴奋性和抑制性突触电导的平衡驱动味觉皮层神经元的味觉反应和形状调节。