Peptide Modulation of Striatal Patch and Matrix Subdivisions

纹状体斑块和基质细分的肽调节

• 批准号: 9125895
• 负责人: Bernardo L Sabatini
• 金额: $ 41.75万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9125895
• 关键词: Acute; Axon; Basal Ganglia; Behavior; Biochemical; Biology; Brain; Cell Nucleus; Cells; Cholecystokinin; Corpus striatum structure; Coupled; Cyclic AMP-Dependent Protein Kinases; Development; Diffuse; Disease; Dopamine; Dorsal; Drug Addiction; Dynorphins; Electrophysiology (science); Enkephalins; Equilibrium; Genetic; Glutamates; Goals; Health; Heart; Human; Huntington Disease; In Vitro; Individual; Laboratories; Light; Neuromodulator; Neurons; Neuropeptides; Neurophysiology - biologic function; Neurotransmitters; Opioid; Opioid Receptor; Optics; Parkinson Disease; Pathway interactions; Pattern; Peptide Receptor; Peptide Signal Sequences; Peptides; Pharmaceutical Preparations; Physiologic pulse; Play; Process; Property; Proteins; Reagent; Receptor Activation; Regulation; Research; Rodent; Role; Route; Signal Pathway; Signal Transduction; Site; Slice; Somatostatin; Staging; Structure; Substance P; Synapses; Synaptic Transmission; System; Therapeutic; Tissues; Transgenic Mice; Work; analog; base; brain cell; brain tissue; cellular targeting; gamma-Aminobutyric Acid; human disease; improved; in vivo; insight; motor control; neuropeptide Y; neuropsychiatric disorder; neuropsychiatric symptom; neurotransmission; neurotransmitter release; new technology; novel; optogenetics; receptor coupling; receptor expression; striosome; synaptic function; tool; two-photon

DESCRIPTION (provided by applicant): The mammalian brain, including the human brain, contains dozens of peptides that act as neurotransmitters between cells but whose function and modes of action are relatively unknown. This is particularly true in the basal ganglia in which the expression of peptides and of peptide receptors varies from cell to cell and nucleus to nucleus. The basal ganglia play a central role in controlling motor action selection - i.e. deciding what we do - and are at the heart of human disorders such as Parkinson's, Huntington's and drug addiction. We propose to study the function of peptides in the basal ganglia in order to understand how they signal and control the circuitry of this structure. We will make use of new technology developed in the laboratory that allows us to precisely release peptides in mammalian brain tissue using pulses of light. This will be used to analyze peptide function in tissue in which specific classes of neurons are marked or placed under optogenetic control. The proposed work will shed light on the basic biology of this conserved signaling system and will inform how its perturbation contributes to disease.

描述(申请人提供)：哺乳动物的大脑，包括人脑，含有数十种多肽，它们充当细胞之间的神经递质，但其功能和作用模式相对未知。这在基底神经节尤其如此，在那里 多肽和多肽受体的表达因细胞和细胞核的不同而不同。基底节在控制运动动作选择中起着中心作用--即决定我们 而且是帕金森氏症、亨廷顿氏症和毒瘾等人类疾病的核心。我们建议研究基底节中多肽的功能，以了解它们是如何发出信号并控制这一结构的回路的。我们将利用实验室开发的新技术，利用光脉冲在哺乳动物脑组织中精确释放多肽。这将被用来分析特定类别的神经元被标记或置于光遗传控制下的组织中的肽功能。这项拟议的工作将阐明这一保守信号系统的基本生物学，并将揭示其扰动如何导致疾病。