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

描述（由申请人提供）：在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。从清醒行为的大鼠的慢性细胞外记录显示一个动态和分布式代码4-10。该模型强调了作为动态集合的广泛调谐神经元群之间独特的时空活动模式。然而，最近来自麻醉小鼠体内钙成像的数据显示了皮层中原始味觉的精确味觉图。这表明了一个编码方案的敏锐调谐味觉皮层神经元排列在地形组织簇。虽然有组织的皮层地图代表初级味觉的证据很有趣，但对这种地图的热情由于对麻醉动物的依赖而减弱了1-3。众所周知，麻醉会引起异常的人工皮层网络动力学，显著影响感觉刺激的处理11。这个提议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的调谐和地形组织。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，以及一种新颖的头部约束小鼠制备方法来实现，该方法可以精确和系统地针对清醒行为小鼠的整个味觉皮层的记录。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层的功能组织，从网络水平到详细的突触机制。

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.