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Development and physiology of axo-axonic synapses

轴突突触的发育和生理学

基本信息

批准号：
9357703
负责人：
Kevin J Bender
金额：
$ 23.78万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-24 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9357703
关键词：
Action Potentials Acute Address Adolescence Adolescent Adolescent Development Adult Affect Age Anatomy Axon Bipolar Disorder Brain Brain region Cell Polarity Cell physiology Cells Chlorides Complement Conflict (Psychology)Data Decision Making Dendrites Development Developmental Delay Disorders Diagnosis Disease Drops Electrophysiology (science)Evaluation Executive Dysfunction Exhibits Frequencies Gated Ion Channel Generations Genetic Genetic Techniques Glutamates Goals Human Image Imaging Techniques Interneurons Ion Channel Gating Lead Life Mediating Membrane Potentials Mental disorders Mus Neurons Optics Parvalbumins Pattern Physiology Positioning Attribute Postsynaptic Membrane Prefrontal Cortex Property Psychiatric therapeutic procedure Pyramidal Cells Regulation Reporting Rest Risk Risk Assessment Rodent Rodent Model Role Sampling Schizophrenia Shunt Device Site Slice Sodium-Potassium-Chloride Symporters Synapses Techniques Testing Third Pregnancy Trimester Time Tissues Work chloride-cotransporter potassium cognitive function executive function gamma-Aminobutyric Acid infancy insight nervous system disorder novel therapeutic intervention novel therapeutics postnatal postsynaptic preadolescence subcellular targeting synaptic function therapeutic target two-photon voltage

项目摘要

During adolescence, many high-order cognitive functions develop and mature, including impulse control, long-term planning, and risk evaluation. Neurological disorders that impair executive function, such as schizophrenia, are often diagnosed during adolescence. One major site of adolescent maturation in prefrontal cortex are GABAergic inhibitory circuits, including parvalbumin positive chandelier cells. Chandelier cells synapse directly onto the axon potential initiating sites of neighboring glutamatergic pyramidal cells. They are therefore uniquely poised to regulate pyramidal cell spiking. Here, our goal is to understand how chandelier cells regulate the activity of pyramidal cells as prefrontal cortical networks undergo adolescent development. We will use a combination of electrophysiology, including perforated patch recording, 2-photon imaging and genetic techniques to understand how these unique interneurons regulate the integrative properties of the axon initial segment. Results of this study will provide insight into how inhibitory circuit maturation contributes to the normal maturation of prefrontal circuits and may elucidate potential therapeutic targets in neurological disorders such as schizophrenia.

在青春期，许多高级认知功能都会发展和成熟，包括冲动控制、长期计划和风险评估。损害执行功能的神经障碍，例如精神分裂症，通常在青春期被诊断出来。前额叶是青春期成熟的主要部位之一大脑皮层是GABA能抑制回路，包括小白蛋白阳性的吊灯细胞。枝形吊灯单元突触直接与邻近谷氨酸能锥体细胞的轴突潜在起始点相连。他们是因此独一无二地准备好调节锥体细胞的尖峰。在这里，我们的目标是了解枝形吊灯当前额叶皮质网络经历青春期发育时，细胞调节锥体细胞的活动。我们将使用电生理学的组合，包括穿孔贴片记录，双光子成像和基因技术以了解这些独特的中间神经元如何调节轴突起始节段。这项研究的结果将为了解抑制回路成熟是如何贡献的提供洞察。前额叶环路的正常成熟，并可能阐明神经学的潜在治疗靶点精神分裂症等精神障碍。