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

皮质 D1R 表达神经元在基于味觉的感觉运动转换中的作用

• 批准号: 10535972
• 负责人: John Chen
• 金额: $ 3.91万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10535972
• 关键词: Affect; Animals; Anterior; Behavior; Behavioral; Bilateral; Brain; Brain region; Calcium; Cells; Code; Cues; Decision Making; Dopamine; Dopamine D1 Receptor; Eating Disorders; Electrophysiology (science); Exhibits; Fire - disasters; Functional disorder; Goals; Image; Individual; Ingestion; Instruction; Knowledge; Laboratories; Lasers; Lateral; Learning; Left; Link; Literature; Maltose; Mastication; Mediating; Methods; Modeling; Monitor; Motor; Motor Cortex; Movement; Mus; Nature; Neuromodulator; Neurons; Opsin; Palate; Pathologic Processes; Pattern; Performance; Pharmacology; Physiological Processes; Play; Population; Preparation; Process; Quinine; Reaction Time; Receptor Inhibition; Receptor Signaling; Reporter; Rewards; Role; Sampling; Sensory; Signal Transduction; Stimulus; Sucrose; Taste Perception; Techniques; Testing; Time; Viral Vector; Work; antagonist; base; cell type; cognitive process; experimental study; insight; neuropsychiatric disorder; neurotransmission; novel; optical imaging; optogenetics; orofacial; receptor; receptor function; relating to nervous system; response; sensory input; sensory stimulus; sucrose octaacetate; taste stimuli; transmission process; two-photon

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.

项目概要 为了生存，动物必须使用味觉刺激来通知和指导以奖励为导向的行为，例如 舔和咀嚼。先前研究这一过程（称为感觉运动整合）的工作已经建立 前外侧运动皮层（ALM）作为模型大脑区域来研究与以下相关的感觉运动处理 舔。该区域内的神经活动反映了舔的感觉信息和运动计划，暗示 ALM 调解基于感觉的舔决策。然而，ALM 是否参与味觉引导仍然未知。 感觉运动整合——尽管舔和味觉总是相关的——以及这个过程是否- 涉及多巴胺能回路。已发现 ALM 内 D1R 信号传导的阻断会影响感觉 刺激引导舔舐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换中表达 D1R（D1R+ 神经元）。然而， D1R+ 神经元在味觉引导的感觉运动整合中的作用尚未得到研究。这项提议将考验中央 假设 D1R+ 神经元在味觉感觉运动转化过程中是必需的，并表现出以下模式： 代表味觉处理和舔选择准备的活动。拟议的实验将依赖于 最近建立的 4 种口味、2 种选择 (2-AC) 任务，其中小鼠必须采样四种中的一种 来自中央的促味剂（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） 喷出并将具有相反感知品质的配对与特定动作（即蔗糖或奎宁 → 舔 左 vs 麦芽糖和蔗糖八乙酸酯 → 舔右）延迟期后。研究 D1R+ 神经元的作用 在这个行为中，我将利用尖端技术的组合，包括细胞类型特定的光基因学 网络操纵和 2 光子钙成像。据我所知，这些将是一些首批实验 检查味觉感觉运动处理和表达 D1R 的神经元之间的联系。