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

描述（由申请人提供）：在初级味觉皮层中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的神经元组之间的活动的独特的空间/时间模式。然而，最近使用体内钙成像的麻醉小鼠的数据显示了皮质中初级味觉的精确味觉图1。这表明了一个编码方案的急剧调整味觉皮层神经元排列在地形组织集群。虽然有组织的皮质地图代表主要口味的证据是耐人寻味的，这样一个地图的热情是由依赖麻醉动物1-3缓和。众所周知，麻醉会导致异常和人工皮层网络动力学，显著影响感官刺激的处理11。这个建议将解决这个问题，直接测试的一般假设，味觉反应神经元的味觉皮层清醒的行为小鼠是狭窄的调整和地形组织。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，与一种新的头部限制的小鼠制备，允许精确和系统的目标记录整个味觉皮层清醒的行为小鼠。具体目标将研究清醒行为动物味觉皮层的功能组织，从网络水平到详细的突触机制，都是前所未有的细节。 目的1：清醒状态下小鼠味觉皮层的味觉反应被严格调节并在功能上组织成地形簇。 目标2：单单位味觉反应反映映射的多单位活动。 目的3：兴奋性和抑制性突触传导的平衡驱动味觉皮层神经元的味觉反应和形状调谐。

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.