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

描述(由申请人提供)：初级味觉皮质中化学刺激编码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，这是一个动态的、分布式的代码4-10。这个模型强调了作为动态集合的一组广泛调谐的神经元之间独特的活动空间/时间模式。然而，来自麻醉小鼠的体内钙成像的最新数据显示了皮层1主要味觉的精确味觉地图。这表明了一种编码方案，该编码方案将味觉皮质神经元急剧调谐排列在地形图组织的簇中。尽管代表初级口味的有组织的皮质地图的证据很耐人寻味，但对这种地图的热情因依赖麻醉的动物1-3而减弱。众所周知，麻醉会导致异常的人工皮质网络动力学，显著影响感觉刺激的处理11。这一提议将通过直接测试一般假设来解决这个问题，该假说认为来自清醒行为的小鼠味觉皮质的味觉反应神经元是狭窄的调谐和地形图组织的。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来实现，以及一种新型的头部约束小鼠制剂，该制剂允许在清醒行为的小鼠的整个味觉皮质中精确和系统地定位记录。具体目标将以前所未有的细节研究清醒行为动物的味觉皮质的功能组织，从网络水平到详细的突触机制。 目的1：在清醒行为的小鼠中，味觉皮层的味觉反应被狭隘地调谐，并在功能上组织成地形簇。 目的2：单一单位的味觉反应反映了映射的多单位活动。 目的3：兴奋性和抑制性突触电导的平衡驱动味觉皮质神经元的味觉反应和形状调节。 与公共健康相关：在美国，糖尿病是一个普遍且代价高昂的公共健康问题。更好地了解甜味食品的味道系统和加工过程将有助于我们制定更好的、科学指导的公共营养政策，以减少儿童和成人的2型糖尿病。

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. PUBLIC HEALTH RELEVANCE: Diabetes is a widespread and costly public health problem in the US. A better understanding of the taste system and processing of sweet tasting foods will help us enact better, scientifically guided, policies for public nutrition, with the goal of reducig childhood and adult type-2 diabetes.