Peptide Modulation of Striatal Patch and Matrix Subdivisions

纹状体斑块和基质细分的肽调节

基本信息

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
项目类别：
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

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

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项目摘要

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（由申请人提供）：包括人脑在内的哺乳动物大脑包含数十种肽，它们在细胞之间充当神经递质，但其功能和作用方式相对尚不清楚。在基底神经节中尤其如此肽和肽受体的表达因细胞到细胞和细胞核而异。基底神经节在控制运动动作选择方面起着核心作用 - 即决定我们什么做 - 并且是帕金森氏症，亨廷顿和吸毒等人类疾病的核心。我们建议研究肽在基底神经节中的功能，以了解它们如何发出信号和控制该结构的电路。我们将利用实验室开发的新技术，使我们能够使用光脉冲在哺乳动物脑组织中精确释放肽。这将用于分析组织中特定类别的神经元的肽功能，以将特定类别的神经元标记或放置在光遗传内。拟议的工作将阐明该保守信号系统的基本生物学，并将告知其扰动如何对疾病有效。