Neurotransmitter plasticity and regulation of behavior

神经递质可塑性和行为调节

• 批准号: 10445855
• 负责人: Leslie C Griffith
• 金额: $ 40.63万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-15 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10445855
• 关键词: Address; Adopted; Adult; Arousal; Behavior; Biology; Cells; Chemicals; Complex; Development; Differentiated Gene; Dopamine; Drosophila genus; Equilibrium; Event; Exhibits; Failure; Functional Imaging; Genetic; Genetic Transcription; Glutamates; Homeostasis; Human; Inbreeding; Individual; Learning; Life; Link; Locomotion; Mammals; Mediating; Memory impairment; MicroRNAs; Molecular; Nervous system structure; Neurons; Neurotransmitters; Pathway interactions; Phenotype; Photoperiod; Physiology; Population; Prevalence; Process; Pupa; Reagent; Regulation; Role; Seizures; Side; Signal Transduction; Site; Sleep; Specific qualifier value; Stress; Synapses; System; Testing; Thinking; Time; Ursidae Family; Variant; Work; base; cholinergic; experimental study; fly; heart function; insight; neurochemistry; neurotransmitter release; novel; programs; recruit; relating to nervous system; response; transcriptome sequencing

Project Summary Neurons have classically been defined by the neurotransmitter they release. This “identity” has been considered to be both singular (i.e. one transmitter) and immutable (i.e. genetically hardwired). While the astonishing prevalence of cotransmission has changed thinking about the singularity of neurotransmitter identity there has been considerably less appreciation of the ability of neurons to exhibit plasticity in their expression. Recently, we discovered that the microRNA miR-190 is a potent regulator of adult sleep. Spatial and temporal mapping of its site of action demonstrates that it is required during pupation in a population of cells that transcribes both cholinergic and glutamatergic genes but differentiates to become a small subset of the adult glutamatergic neurons. This subset includes components of the core sleep homeostasis circuit. We will test the hypothesis that a neurotransmitter plasticity event is critical to function of the mature circuit and that it provides a novel mechanism for establishing, and potentially modifying, the sleep set-point of the homeostatic machinery. Aim 1 will determine the role of neurotransmitter plasticity in the control of adult sleep, with a focus on understanding the circuit-level changes. Aim 2 will investigate the role of neuronal activity in transmitter switching and homeostat plasticity, with a focus on understanding the molecular events. In this proposal, we bring the power of Drosophila genetics to bear on this novel and important type of plasticity. We demonstrate that programmed transmitter plasticity during pupal life is crucial to adult function of the sleep circuitry. The genetic reagents we have developed will allow us to address basic mechanisms underlying transmitter plasticity in the context of both the developing and mature nervous systems and, for the first time, link this type of plasticity to sleep.

项目摘要 神经元通过它们释放的神经递质经典定义。这种“身份”具有 被认为是奇异的（即一个发射器），又是不变的（即遗传上的 硬线）。尽管共晶的惊人患病率已经改变了思考 神经递质身份的奇异性已经被认为是对该神经递质的认识 神经元在表达中暴露可塑性的能力。最近，我们发现 microRNA mir-190是成人睡眠的潜在调节剂。其网站的空间和临时映射 作用表明，在转录的细胞种群中化合了时需要它 胆碱能和谷氨酸能基因都有区分成为一小部分 成人谷氨酸能神经元。该子集包括核心睡眠稳态的组成部分 电路。我们将检验以下假设：神经递质可塑性事件对于功能至关重要 成熟的电路及其提供了一种新颖的机制，可以建立和可能 修改，稳态机械的睡眠设定点。 AIM 1将确定神经递质可塑性在控制成人睡眠中的作用， 专注于了解电路级别的变化。 AIM 2将研究神经元活性在发射器开关和体内平移中的作用 可塑性，重点是理解分子事件。 在此提案中，我们将果蝇遗传学的力量赋予了这部小说而重要的 可塑性的类型。我们证明了pupal寿命期间编程的发射器可塑性是 对睡眠电路的成人功能至关重要。我们开发的遗传试剂将允许 在两者的背景下，我们解决发射机可塑性的基本机制 开发和成熟的神经系统，这是第一次将这种可塑性联系起来 睡觉。