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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

基本信息

批准号：
10815224
负责人：
Benjamin Kyle Scholl
金额：
$ 2.64万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
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/10815224
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

项目摘要

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.

雪貂视皮层单层2/3神经元的突触前网络原理新皮质环路中的单个神经元由兴奋性神经元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对传入的信息进行处理。长期以来，对大脑皮层回路的一种看法是，大多数突触输入通过水平(循环)连接来自局部网络。然而，递归网络塑造皮质神经元活动的机制是很大程度上是未知的。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质的研究，越来越多的研究表明，这与食肉动物和灵长类动物在组织和功能上。拟议的职业发展计划目的是通过定位单个神经元的突触前兴奋性和抑制性细胞来解决这些问题 2/3层神经元及其如何选择性地调节雪貂V1的神经活动在活体内。该方案使用了先进的光学技术和电生理学。应聘者在体内生理学和光学成像方面有深厚的背景在种类繁多的哺乳动物中。应聘者提议接受有关国家的培训。最先进的多光子全息光遗传学和新型分子工具的使用。候选人还将从导师和顾问那里获得职业发展方面的指导。这次培训将建立成功的独立研究生涯所需的技能学习的角色非小鼠模型系统中基本皮层操作中突触前网络的研究。这个候选人将在世界知名的大卫·菲茨帕特里克博士的指导下分阶段进行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。这个候选人将由多光子全息术的先驱希勒尔·阿德斯尼克博士共同指导光遗传学和应聘者建议使用的开发技术。补充建议来自 Kristina Nielsen博士和Krishnan Padmanabhan博士将提供专业指导发展和向学术地位的过渡。MPFI将提供出色的研究环境，拥有丰富的资源、技术支持和与杰出科学家帮助确保成功完成拟议的研究和过渡为独立干杯。候选人的长期抱负是建设一个创新和建立大脑皮层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障碍提供了一个支架，这表明在处理感官信号方面存在严重的障碍。