The role of cortical D1R-expressing neurons in taste-based sensorimotor transformations

项目摘要 为了生存，动物必须使用味觉感官刺激来通知和指导奖励导向的行为， 舔和咀嚼。以前的工作研究这个过程，被称为感觉运动整合，已经建立了 前外侧运动皮层（ALM）作为模型脑区研究感觉运动加工相关的 舔该区域的神经活动反映了舔的感觉信息和运动规划， ALM介导基于感觉的舔决策。然而，它仍然是未知的，如果ALM参与口味引导， 感觉运动整合--尽管舔和味觉总是联系在一起--以及这个过程是否-- 控制多巴胺能回路已经发现ALM内D1 R信号传导的阻断影响感觉和感觉神经。 刺激引导的舔的诱发反应和运动规划，表明ALM神经元的潜在作用 在舔相关的感觉运动转化中表达D1 R（D1 R+神经元）。然而， D1 R+神经元在味觉引导的感觉运动整合仍然没有研究。这一提议将考验中央 假设D1 R+神经元在味觉感觉运动转化过程中是必需的，并表现出 代表味觉加工和舔选择准备的活动。拟议的实验将依赖于 最近建立的4种味道，2种选择（2-AC）任务，其中小鼠必须从四个中选择一个 促味剂（即，两种甜味剂：蔗糖、麦芽糖和两种苦味剂：奎宁和蔗糖八乙酸酯） 将具有相反感知品质的对与特定动作相关联（即，蔗糖或奎宁→舔 左vs麦芽糖和蔗糖八乙酸酯→舔右）。研究D1 R+神经元在脑缺血中的作用 在这一行为中，我将利用尖端技术的组合，包括细胞类型特异性光基因， 遗传操作和双光子钙成像。据我所知，这些将是第一批实验 研究味觉感觉运动处理和表达D1 Rs的神经元之间的联系。

PROJECT SUMMARY To survive, animals must use gustatory sensory stimuli to inform and guide reward-oriented actions like licking and chewing. Previous work examining this process, known as sensorimotor integration, has established the anterior lateral motor cortex (ALM) as a model brain region to study sensorimotor processing related to licking. Neural activity within this region reflects sensory information and motor planning of licking, implicating ALM in mediating sensory-based lick decisions. However, it remains unknown if ALM is involved in taste-guided sensorimotor integration – despite licking and taste being invariably connected – and whether this process in- volves dopaminergic circuits. Blockade of D1R signaling within ALM has been found to affect both sensory- evoked responses and motor planning of stimuli-guided licking, suggesting a potential role for ALM neurons expressing D1Rs (D1R+ neurons) in lick-related sensorimotor transformations. However, the contributions of D1R+ neurons in taste-guided sensorimotor integration remains unstudied. This proposal will test the central hypothesis that D1R+ neurons are required during gustatory sensorimotor transformation and exhibit patterns of activity representing gustatory processing and preparation of lick choice. The proposed experiments will rely on a recently established 4-taste, 2-alternative choice (2-AC) task in which mice must sample one out of four tastants (i.e., two sweets: sucrose, maltose and two bitters: quinine and sucrose octaacetate) from a central spout and associate pairs with opposite perceptual qualities with specific actions (i.e., sucrose or quinine → lick left vs maltose and sucrose octaacetate → lick right) after a delay period. To study the role of D1R+ neurons during this behavior, I will utilize a combination of cutting-edge techniques that include cell-type specific optoge- netic manipulation and 2-photon calcium imaging. To my knowledge, these will be some of the first experiments examining the link between gustatory sensorimotor processing and neurons expressing D1Rs.