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.

项目总结 为了生存，动物必须使用味觉刺激来通知和引导以奖励为导向的行为，如 又舔又嚼。以前研究这一过程的工作，即所谓的感觉运动整合，已经确定 以前外侧运动皮质(ALM)为模型脑区研究感觉运动相关加工 在舔。该区域内的神经活动反映了舔、暗示的感觉信息和运动计划 ALM在调节基于感觉的舔决策中的作用。然而，目前尚不清楚ALM是否参与了味觉指导 感觉运动集成-尽管舔和味道总是联系在一起-以及这个过程是否在- 传递多巴胺能神经回路。研究发现，在ALM内阻断D1R信号会影响两种感觉- 刺激引导舔舔的诱发反应和运动规划，提示ALM神经元的潜在作用 在舔相关感觉运动转化中表达D1R(D1R+神经元)。然而，中国的贡献 D1R+神经元在味觉引导的感觉运动整合中仍未被研究。这项提议将考验中央银行 假设D1R+神经元在味觉感觉运动转换过程中是必需的，并显示出 代表味觉加工和舔舔选择准备的活动。拟议中的实验将依赖于 最近建立的4味2选一(2-AC)任务，小鼠必须从四个中选择一个 品尝(即，两种糖：蔗糖，麦芽糖和两种苦味：奎宁和蔗糖八醋酸酯) 吐出并将具有相反感知特性的配对与特定动作(即蔗糖或奎宁→舔)联系在一起 左VS麦芽糖和蔗糖八醋酸酯→在延迟时间后舔右)。研究D1R+神经元的作用 在这一行为中，我将利用尖端技术的组合，包括细胞类型的特定光学- 磁操纵和双光子钙成像。据我所知，这些将是最初的一些实验 研究味觉感觉运动处理和表达D1Rs的神经元之间的联系。