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，许多高阶认知功能发展并成熟，包括冲动控制、长期规划和风险评估。损害执行功能的神经系统疾病，例如精神分裂症通常在青春期被诊断出来。青少年成熟的主要部位之一是前额叶皮层有GABA能抑制电路，包括小白蛋白阳性吊灯细胞。枝形吊灯单元突触直接连接到邻近谷氨酸能锥体细胞的轴突电位起始位点。他们是因此具有独特的调节锥体细胞尖峰的能力。在这里，我们的目标是了解吊灯如何当前额皮质网络经历青少年发育时，细胞调节锥体细胞的活动。我们将结合使用电生理学，包括穿孔贴片记录、2 光子成像和遗传技术来了解这些独特的中间神经元如何调节神经元的整合特性轴突起始段。这项研究的结果将深入了解抑制电路成熟如何发挥作用促进前额叶回路的正常成熟，并可能阐明神经系统的潜在治疗靶点精神分裂症等疾病。