RIG: Role of sustained GABA in light-induced phase shifts of the circadian pacemaker

RIG：持续 GABA 在光诱导昼夜节律起搏器相移中的作用

• 批准号: 1022050
• 负责人: Daniel Hummer
• 金额: $ 20万
• 依托单位: Morehouse College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1022050&HistoricalAwards=false
• 关键词: RIG; Role; sustained; GABA; light

The mammalian brain contains a biological clock that generates behavioral and physiological rhythms that are close to, but not exactly 24 hours. For organisms to synchronize these internally generated circadian rhythms to the 24-hour environment, the clock must be adjusted each day through exposure to light. The mechanism through which light is able to adjust the timing of the biological clock is not fully understood. The central aim of this proposal is to test the hypothesis that sustained activation of receptors for ã-aminobutyric acid (GABA) mediates the ability of light to shift the daily rhythms generated by the biological clock. Utilizing an in vivo pharmacological approach in hamsters, small quantities of drugs that either mimic or block GABA activity will be delivered over several hours to the region of the brain that contains the biological clock. The effect of these drugs on circadian rhythms will be determined by measuring the daily activity rhythms of hamsters given access to running wheels. It is expected that long-term administration of GABA-like drugs will shift the daily activity rhythms of hamsters in a manner similar to light, and that the administration of drugs that block the activity of GABA will prevent the ability of light to shift the daily activity rhythms generated by the biological clock. Results from this research will provide insight into a fundamental process by which organisms synchronize or entrain their biological rhythms to a cyclical environment. This research has important implications for understanding how shift work and trans-Atlantic travel alter biological rhythms in humans (e.g., jet lag). Furthermore, the proposed activities will take place at, and involve undergraduates from Morehouse College (a historically black undergraduate institution in Atlanta, Georgia), thus broadening the participation of African American males in biology.

哺乳动物的大脑包含一个生物钟，产生接近但不完全是24小时的行为和生理节律。 为了使生物体将这些内部产生的昼夜节律与24小时的环境同步，生物钟必须每天通过暴露于光来调整。 光能够调节生物钟时间的机制尚未完全了解。 该提案的中心目的是验证以下假设：持续激活γ-氨基丁酸（GABA）受体介导光改变生物钟产生的每日节律的能力。 利用仓鼠体内药理学方法，将模拟或阻断GABA活性的少量药物在几个小时内递送到包含生物钟的大脑区域。 这些药物对昼夜节律的影响将通过测量仓鼠的日常活动节律来确定。 预期长期给予GABA样药物将以类似于光的方式改变仓鼠的日常活动节律，并且给予阻断GABA活性的药物将阻止光改变生物钟产生的日常活动节律的能力。 这项研究的结果将提供一个基本的过程，生物体同步或夹带其生物节律的周期性环境的洞察力。 这项研究对于理解轮班工作和跨大西洋旅行如何改变人类的生物节律具有重要意义（例如，时差）。 此外，拟议的活动将在莫尔豪斯学院（格鲁吉亚亚特兰大的一所历史上的黑人本科院校）举行，并有莫尔豪斯学院的本科生参加，从而扩大非洲裔美国男子对生物学的参与。