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 神经元通常由它们释放的神经递质来定义。这个“身份”， 被认为是单一的（即一个发射机）和不可变的（即遗传 硬连线）。虽然共同传播的惊人流行改变了人们对艾滋病的看法， 神经递质身份的单一性， 神经元在其表达中表现出可塑性的能力。最近，我们发现， microRNA miR-190是成年人睡眠的有效调节因子。网站的空间和时间映射 的行动表明，它是需要在化蛹过程中的细胞群体，转录 胆碱能和谷氨酸能基因，但分化成为一个小的子集， 成年海马神经元这个子集包括核心睡眠稳态的组成部分 电路.我们将检验神经递质可塑性事件对神经系统功能至关重要的假设。 成熟的电路，它提供了一个新的机制，建立，并可能 改变自我平衡机制的睡眠设定点。 目标1将确定神经递质可塑性在成人睡眠控制中的作用，并 专注于理解电路级的变化。 目的2将研究神经元活动在递质转换和稳态中的作用 可塑性，重点是了解分子事件。 在这个提议中，我们将果蝇遗传学的力量运用到这个新颖而重要的领域。 可塑性的类型我们证明，在蛹的生活程序化的递质可塑性， 对成年人的睡眠回路功能至关重要。我们研发的基因试剂 我们要解决的基本机制，潜在的递质可塑性的背景下， 发展和成熟的神经系统，并首次将这种类型的可塑性与 睡吧