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: 10652395
• 负责人: John Chen
• 金额: $ 4万
• 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/10652395
• 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; Knowledge; Laboratories; Lasers; Lateral; Learning; Left; Link; Literature; Maltose; Mastication; Mediating; Methods; Modeling; Monitor; Motor; Motor Cortex; Movement; Mus; Nature; Neuromodulator; Neurons; Opsin; Pathologic Processes; Pattern; Performance; 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; cell type; cognitive process; comparison control; experimental study; insight; neural; neuropsychiatric disorder; neurotransmission; novel; optical imaging; optogenetics; orofacial; pharmacologic; receptor; receptor function; 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.

项目摘要 为了生存，动物必须使用味觉的感觉刺激来告知和指导奖励的动作 舔和咀嚼。以前检查此过程的工作，称为感觉运动集成，已经建立了 前侧运动皮层（ALM）作为模型的大脑区域，用于研究与 舔。该区域内的神经活动反映了舔的感觉信息和运动计划，这意味着 ALM介导基于感觉的舔决策。但是，尚不清楚ALM是否参与味觉引导 感觉运动的整合 - 渴望舔和味道总是连接的 - 以及该过程是否融入 电压多巴胺能电路。发现ALM内D1R信号传导的封锁会影响两种感觉 - 诱发刺激引导的舔的反应和运动计划，这表明ALM神经元的潜在作用 在舔相关的感觉运动转化中表达D1RS（D1R+神经元）。但是， 味觉引导的感觉运动整合中的D1R+神经元仍未研究。该建议将测试中央 假设在味觉感觉运动转化和暴露的模式中需要D1R+神经元 代表味道选择的味道加工和制备的活动。拟议的实验将依靠 最近建立的4种泥2-替代选择（2-AC）任务，其中小鼠必须采样四分之一 来自中央 吐口和相关的对具有相反感知质量的相反的作用（即蔗糖或奎宁→舔） 在延迟期间，左右麦芽糖和蔗糖八乙酸→右舔→右）。研究D1R+神经元的作用 在这种行为期间，我将利用包括细胞类型特异性光的尖端技术组合 网络操作和2光子钙成像。据我所知，这些将是第一个实验 检查味觉感觉运动处理与表达D1RS的神经元之间的联系。