Neurotransmitter Plasticity and Regulation of Behavior

神经递质可塑性和行为调节

• 批准号: 10565933
• 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/10565933
• 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; Individual Adjustment; Learning; Life; Link; Locomotion; Mammals; Maps; Mediating; Memory impairment; MicroRNAs; Molecular; Nervous System; Neurons; Neurotransmitters; Pathway interactions; Phenotype; Photoperiod; Physiology; Population; Prevalence; Process; Reagent; Regulation; Role; Seizures; Side; Signal Transduction; Site; Sleep; Specific qualifier value; Stress; Synapses; System; Testing; Thinking; Time; Variant; Work; cholinergic; experimental study; fly; heart function; insight; neural; neurochemistry; neurotransmitter release; novel; programs; recruit; 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.

项目概要 神经元传统上是由它们释放的神经递质来定义的。这个“身份”有 被认为是单一的（即一个发射器）和不可变的（即基因上 硬连线）。虽然共同传播的惊人流行已经改变了人们对这一问题的看法 神经递质特性的奇点性，人们对神经递质特性的认识要少得多 神经元在表达中表现出可塑性的能力。最近，我们发现， microRNA miR-190 是成人睡眠的有效调节剂。其地点的时空映射 作用证明在化蛹期间转录的细胞群中需要它 胆碱能和谷氨酸能基因，但分化成为胆碱能和谷氨酸能基因的一小部分 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神经递质的功能至关重要 成熟的电路，它提供了一种新颖的机制，可以建立并有可能 修改稳态机制的睡眠设定点。 目标 1 将确定神经递质可塑性在成人睡眠控制中的作用， 重点了解电路级的变化。 目标 2 将研究神经元活动在递质转换和稳态中的作用 可塑性，重点是理解分子事件。 在这项提案中，我们将果蝇遗传学的力量应用于这一新颖而重要的研究 可塑性类型。我们证明了蛹生命期间程序化递质的可塑性 对睡眠回路的成人功能至关重要。我们开发的遗传试剂将允许 我们要解决发射机可塑性的基本机制 发育和成熟的神经系统，并首次将这种可塑性与 睡觉。