Principles of presynaptic networks for single layer 2/3 neurons in ferret visual cortex

雪貂视觉皮层单层2/3神经元突触前网络原理

• 批准号: 10675072
• 负责人: Benjamin Kyle Scholl
• 金额: $ 24.08万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10675072
• 关键词: Address; Attenuated; Behavior; Biological Models; Calcium; Cells; Development; Development Plans; Disease; Electrophysiology (science); Elements; Ensure; Environment; Exhibits; Ferrets; Goals; Holography; Image; Impairment; Interdisciplinary Study; Interneurons; Maps; Measures; Membrane Potentials; Mentors; Molecular; Neocortex; Neurons; Optics; Pattern; Phase; Photic Stimulation; Physiological; Physiology; Population; Positioning Attribute; Primates; Process; Property; Recurrence; Research; Resources; Rodent; Role; Schizophrenia; Scientist; Sensory; Shapes; Signal Transduction; Stimulus; Synapses; Target Populations; Techniques; Testing; Theoretical model; Training; Variant; Visual; Visual Cortex; Visual System; aspirate; autism spectrum disorder; career; career development; excitatory neuron; experimental study; in vivo; inhibitory neuron; innovation; insight; multi-photon; neocortical; neural; novel; operation; optical imaging; optogenetics; patch clamp; photoactivation; postsynaptic; postsynaptic neurons; presynaptic; presynaptic neurons; programs; recruit; scaffold; sensory cortex; sensory input; skills; statistics; tool; two-photon; visual stimulus

Principles of presynaptic networks for single layer 2/3 neurons in ferret visual cortex Single neurons in neocortical circuits are driven by presynaptic networks composed of excitatory and inhibitory neurons. Each neuron’s population of presynaptic partners determines how incoming information is processed. A longstanding view of cortical circuits is that a majority of synaptic inputs originate from local networks through horizontal (recurrent) connections. However, the mechanisms by which recurrent networks shape the activity of cortical neurons is largely unknown. Additionally, synaptic and cellular mechanisms proposed by theoretical models rely on studies of the rodent visual cortex, which is increasingly shown to differ from that of carnivores and primates in organization and function. The proposed career development plan aims to address these problems by mapping presynaptic excitatory and inhibitory cells of single layer 2/3 neurons and dissecting how they act to selectively modulate neural activity in ferret V1 in vivo. This proposal uses a novel combination of advanced optical techniques and electrophysiology. The candidate has a deep background in in vivo physiology and optical imaging in a wide variety of mammalian species. The candidate proposes to receive training in state-of- the-art multiphoton holographic optogenetics and the use of novel molecular tools. The candidate will also receive guidance from mentors and advisors on professional development. This training will establish the necessary skills for a successful independent research career studying the role of presynaptic networks in fundamental cortical operations in a non-murine model system. The candidate will carry out the mentored phased under Dr. David Fitzpatrick, a world-prominent expert on the early visual-system and cortical processing of carnivores and primates. The candidate will be co-mentored by Dr. Hillel Adesnik, who is a pioneer in multiphoton holographic optogenetics and developed techniques the candidate proposes to use. Additional advising from Dr. Kristina Nielsen and Dr. Krishnan Padmanabhan will provide guidance in professional development and the transition to an academic position. MPFI will provide an excellent research environment, with abundant resources, technical support, and intellectual discussions with prominent scientists to help ensure successful completion of the proposed research and transition to independence. The candidate’s long-term aspirations are to build an innovative and multidisciplinary research program to establish fundamental principles of cortical circuits, ultimately providing a scaffold for understanding disorders, such as schizophrenia and autism, which show profound impairments in the processing of sensory signals.

雪貂视觉皮层中单层2/3神经元的突触前网络原理 新皮质电路中的单神经元是由兴奋性驱动的突触前网络驱动的 和抑制神经元。每个神经元的突触前伴侣的人群都决定了如何 处理信息已处理。长期以来对皮质电路的看法是，大多数 突触输入来自本地网络，通过水平（复发）连接。 但是，复发网络塑造皮质神经元活性的机制是 在很大程度上未知。另外，由理论模型提出的突触和细胞机制 依靠啮齿动物视觉皮质的研究，该研究越来越多地显示出与 组织和功能中的食肉动物和私人。拟议的职业发展计划 旨在通过绘制突触前兴奋和抑制细胞来解决这些问题 第2/3层神经元，并解剖它们如何作用以选择性调节雪貂V1中的神经元活性 体内。该建议使用了高级光学技术和 电生理学。候选人在体内生理和光学成像方面具有深厚的背景 在多种哺乳动物中。候选人提议接受有关最新培训的培训 Art多光子全息光遗传学和新型分子工具的使用。候选人 还将获得导师和专业发展顾问的指导。这个培训 将为成功研究角色的成功独​​立研究职业建立必要的技能 非毛线模型系统中基本皮质操作的突触前网络的。这 候选人将在世界占主导地位的戴维·菲茨帕特里克（David Fitzpatrick）博士的带领下进行分阶段 食肉动物和私人的早期视觉系统和皮质处理的专家。 候选人将由Hillel Adesnik博士共同出庭，他是Multiphoton全息图的先驱 光遗传学和开发技术候选提案要使用。来自 Kristina Nielsen博士和Krishnan Padmanabhan博士将提供专业指导 发展和向学术职位的过渡。 MPFI将提供一项出色的研究 环境，具有丰富的资源，技术支持和智力讨论 杰出的科学家，以帮助确保成功完成拟议的研究和过渡 独立。候选人的长期愿望是建立创新和 多学科研究计划，以建立皮质回路的基本原理， 最终提供了理解疾病的脚手架，例如精神分裂症和自闭症， 这在处理信号的处理中显示出严重的损害。