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: 10405877
• 负责人: Benjamin Kyle Scholl
• 金额: $ 24.9万
• 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/10405877
• 关键词: Address; Attenuated; Behavior; Biological Models; Calcium; Cells; Development; Development Plans; Disease; Electrophysiology (science); Elements; Ensure; Environment; Exhibits; Ferrets; Goals; Image; Impairment; Interdisciplinary Study; Interneurons; Maps; Measures; Membrane Potentials; Mentors; Molecular; 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 structure; autism spectrum disorder; career; career development; excitatory neuron; experimental study; in vivo; inhibitory neuron; innovation; insight; neocortical; novel; operation; optical imaging; optogenetics; patch clamp; photoactivation; postsynaptic; postsynaptic neurons; presynaptic; programs; recruit; relating to nervous system; scaffold; 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.

雪貂视觉皮层单层2/3神经元突触前网络原理 新皮质回路中的单个神经元由兴奋性神经网络组成的突触前网络驱动。 和抑制性神经元。每个神经元的突触前伙伴群体决定了如何 处理传入的信息。长期以来对皮质回路的看法是，大多数 突触输入通过水平（循环）连接源自局部网络。 然而，循环网络塑造皮质神经元活动的机制是 很大程度上不为人知。此外，理论模型提出的突触和细胞机制 依赖于对啮齿动物视觉皮层的研究，越来越多的证据表明，啮齿动物视觉皮层与人类的视觉皮层不同 肉食动物和灵长类动物的组织和功能。拟议的职业发展计划 旨在通过绘制单个突触前兴奋性和抑制性细胞来解决这些问题 2/3 层神经元并剖析它们如何选择性地调节雪貂 V1 的神经活动 体内。该提案采用了先进光学技术和 电生理学。候选人在体内生理学和光学成像方面具有深厚的背景 在多种哺乳动物物种中。候选人建议接受以下方面的培训： 最先进的多光子全息光遗传学和新型分子工具的使用。候选人 还将接受导师和顾问的专业发展指导。本次培训 将建立成功的独立研究生涯所需的技能 非小鼠模型系统中基本皮质操作的突触前网络。这 候选人将在世界著名的大卫·菲茨帕特里克博士的指导下进行分阶段的指导 食肉动物和灵长类动物早期视觉系统和皮质处理方面的专家。这 候选人将由多光子全息先驱 Hillel Adesnik 博士共同指导 候选人建议使用的光遗传学和开发技术。额外建议来自 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 将提供出色的研究 环境，拥有丰富的资源、技术支持和智力讨论 杰出科学家帮助确保成功完成拟议的研究和过渡 到独立。候选人的长期愿望是建立一个创新和 建立皮质回路基本原理的多学科研究计划， 最终为理解精神分裂症和自闭症等疾病提供了一个支架， 这显示出感觉信号处理方面的严重障碍。