Controlling the Serotonergic System in Mice by Light

通过光控制小鼠的血清素系统

• 批准号: 6707383
• 负责人: STEFAN HERLITZE
• 金额: $ 33.18万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6707383
• 关键词: action potentials; confocal scanning microscopy; genetically modified animals; hippocampus; laboratory mouse; laboratory rat; membrane channels; membrane potentials; membrane transport proteins; model design /development; neurons; neuroregulation; neurotransmitter transport; photostimulus; potassium channel; rhombencephalon; serotonin; voltage /patch clamp

DESCRIPTION (provided by applicant): A major challenge to understand the relation between neural activity and development and ultimately between neuronal activity and behavior is to be able to control the activity of many nerve cells or regions of individual nerve cells simultaneously. Ideally, a technique for controlling nerve cell activity should be capable of switching nerve cells on or off within milliseconds without injuring the cells. We therefore will develop molecular light switches capable of controlling the membrane potential of cells. Light activated proton channels will be used to trigger depolarization, while either light activated potassium channels or Cl-transporters will be used to induce hyperpolarization. These constructs will first be tested in small neuronal nets from primary hippocampal neurons (introduced via viral infection) to better understand the cellular mechanisms underlying synaptic plasticity. Second, transgenic mice will be created, in which the molecular light switches will be under the control of a promoter specific for serotonergic neurons. Serotonin has been implicated in playing important roles in various physiological functions such as mood, sexual behavior, feeding, sleep/wake cycle, memory and cognition. Furthermore, changes in serotonin levels have been related to several diseases, e.g. depression, anxiety and schizophrenia. Understanding how serotonergic activity is modulating brain function will therefore be highly relevant for understanding behavior of mammals and will ultimately lead to the development of therapeutic approaches to cure dysfunctions of serotonergic transmission.

描述（由申请人提供）：