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Development and physiology of axo-axonic synapses

Development and physiology of axo-axonic synapses
轴突突触的发育和生理学
批准号:
9357703
负责人:
Kevin J Bender
金额:
$23.78万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-09-24 至 2019-08-31

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中文摘要
翻译
在青春期,许多高级认知功能发展和成熟,包括冲动控制,长期计划和风险评估。损害执行功能的神经系统疾病,如 精神分裂症通常在青春期被诊断出来。青少年成熟的一个主要部位是前额叶 皮质是GABA能抑制回路,包括小清蛋白阳性枝形细胞。枝形细胞 突触直接连接到邻近的突触能锥体细胞的轴突潜在起始位点上。他们是 因此能够调节锥体细胞的尖峰。在这里,我们的目标是了解如何吊灯 细胞调节锥体细胞的活动,因为前额叶皮质网络经历青春期发育。 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 遗传技术,以了解这些独特的interneurons如何调节的整合特性, 轴突起始段。这项研究的结果将提供深入了解如何抑制回路成熟有助于 前额叶回路的正常成熟,并可能阐明神经系统疾病的潜在治疗靶点。 精神分裂症等疾病。
英文摘要
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.
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