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GABAergic Signaling in the External Globus Pallidus

苍白球外部的 GABA 信号传导

基本信息

批准号：
9308179
负责人：
Savio Chan
金额：
$ 44.32万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-02-01 至 2022-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9308179
关键词：
Achievement Adult Aging Anatomy Animal Model Basal Ganglia Behavioral Calcium-Binding Proteins Cells Chronic Clinical Computer Simulation Corpus striatum structure Development Disease Dorsal Electrophysiology (science)Elements Event Exhibits Fiber Functional disorder GABA Receptor GABA-A Receptor Genetic Recombination Globus Pallidus Handedness Health Home environment Knowledge Lesion Measures Modeling Molecular Motor Motor output Movement Mus Neurodegenerative Disorders Neurons Opsin Output Parkinson Disease Parvalbumins Pathologic Pathway interactions Patients Pattern Periodicity Photometry Play Research Role Shapes Signal Transduction Stimulus Structure Symptoms Synapses System Techniques Therapeutic Transgenic Organisms Weight density dopaminergic neuron experimental study improved in vivo information processing motor control motor deficit motor symptom nerve supply novel therapeutics optogenetics patch clamp phase change postsynaptic prevent targeted treatment tool transcription factor viral gene delivery voltage clamp

项目摘要

Project Summary Parkinson’s disease (PD) is the second most common neurodegenerative disease associated with aging. The disease is characterized by motor symptoms attributed to the loss of mesencephalic dopaminergic neurons and their innervation to the basal ganglia macrocircuit. In patients and animal models of PD, this macrocircuit exhibits aberrant activity patterns including synchronous, rhythmic bursting of neurons in the external globus pallidus (GPe). However, the factors that shape these synchronous and temporallystructured events in PD remain unknown. It is our overarching hypothesis that GABAergic inputs shape the activity level, pattern, and synchrony of both parvalbumin and Npas1 neurons within the GPe. Using cell and circuitspecific tools, we will investigate the connectivity of striatal inputs and local collateral inputs to parvalbumin and Npas1 neurons within the GPe and how this connectivity becomes altered in the chronic 6OHDA lesion model of PD. Furthermore, we will determine how parvalbumin and Npas1 neurons and their striatal inputs are involved in motor function and dysfunction. The proposed experiments capitalize on a combination of cuttingedge approaches that will overcome obstacles that had impeded progress until now. These approaches include viral gene delivery, Crelox recombination, optogenetics, chemogenetics, electrophysiology, and fiber photometry. Additionally, anatomical, analytical, and computational approaches will be used to help interpret research findings. The successful achievement of these aims will significantly advance our understanding of the mechanisms underlying PD and, in doing so, promote the development of new therapies for PD patients.

项目总结