Investigating dopaminergic neuronal circuits mediating circadian entrainment to scheduled feeding

研究介导昼夜节律与计划喂养的多巴胺能神经元回路

• 批准号: 10093069
• 负责人: Andrew David Steele
• 金额: $ 11.03万
• 依托单位: CALIFORNIA STATE POLY U POMONA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-13 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10093069
• 关键词: Activity Cycles; Address; Age; Arousal; Behavioral; Brain; Caring; Circadian Rhythms; Corpus striatum structure; Development; Disease; Dopamine; Dopaminergic Agents; Dorsal; Eating; Failure; Feeding behaviors; Genetic; Health; Hunger; Hypothalamic structure; Knock-out; Knockout Mice; Link; Mediating; Mediator of activation protein; Medical; Mouse Strains; Mus; Neurons; Neurotransmitters; Physiological; Population; Production; Research; Schedule; Signal Transduction; System; Testing; Therapeutic; United States; circadian; cost; dopaminergic neuron; feeding; feeding schedule; genetic approach; neuronal circuitry; receptor

Project Summary This project follows up on our recent research implicating the neurotransmitter dopamine signaling as key mediator of circadian timing systems. Our main hypothesis is a subpopulation of dopaminergic neurons send signals to a population of dopamine type 1 receptor 1 (D1r)-expressing neurons in the dorsal striatum, constituting a critical link between food intake and circadian rhythms of daily activity. To address this hypothesis we propose to generate several genetically modified mice and test their behavioral and physiological entrainment to scheduled feeding. These results will expand our understanding of how the downstream targets of dopamine neurons control several important aspects of feeding related behaviors. In addition, since there are numerous dopaminergic drugs available, this research may suggest potential therapeutic strategies to target diseases associated with over- and under-eating.

项目摘要 该项目是我们最近涉及神经递质多巴胺的研究的后续研究 信号作为昼夜节律计时系统的关键介质。我们的主要假设是 多巴胺能神经元亚群向多巴胺1型神经元群发送信号 受体1（D1r）表达神经元在背侧纹状体，构成了一个关键环节 食物摄入和日常活动的昼夜节律之间的联系。为了解决这个假设 我们建议生产几只转基因小鼠，并测试它们的行为和 生理上的牵引到预定的进食。这些结果将扩大我们的 了解多巴胺神经元的下游靶点如何控制几个 喂养相关行为的重要方面。此外，由于有许多 多巴胺能药物可用，这项研究可能会提出潜在的治疗策略 针对与进食过量和不足有关的疾病。

项目成果

Food anticipatory activity on a calorie-restricted diet is independent of Sirt1.

• DOI: 10.1371/journal.pone.0199586
• 发表时间: 2018
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Assali DR;Hsu CT;Gunapala KM;Aguayo A;McBurney M;Steele AD
• 通讯作者: Steele AD

Type 1 dopamine receptor (D1R)-independent circadian food anticipatory activity in mice.

• DOI: 10.1371/journal.pone.0242897
• 发表时间: 2021
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Assali DR;Sidikpramana M;Villa AP;Falkenstein J;Steele AD
• 通讯作者: Steele AD

Mice hypomorphic for Pitx3 show robust entrainment of circadian behavioral and metabolic rhythms to scheduled feeding.

• DOI: 10.1016/j.celrep.2021.109865
• 发表时间: 2022-01-11
• 期刊: Cell reports
• 影响因子: 8.8
• 作者: Scarpa LL;Wanken B;Smidt M;Mistlberger RE;Steele AD
• 通讯作者: Steele AD

Food Anticipatory Activity on Circadian Time Scales Is Not Dependent on Central Serotonin: Evidence From Tryptophan Hydroxylase-2 and Serotonin Transporter Knockout Mice.

• DOI: 10.3389/fnmol.2020.534238
• 发表时间: 2020
• 期刊: Frontiers in molecular neuroscience
• 影响因子: 4.8
• 作者: Gallardo CM;Martin CS;Steele AD
• 通讯作者: Steele AD