Nucleus reuniens of the thalamus as a target for driving network-wide memory states

丘脑核团聚作为驱动网络范围内存状态的目标

• 批准号: 10736864
• 负责人: Tatiana Danela Viena
• 金额: $ 13.39万
• 依托单位: FLORIDA INTERNATIONAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10736864
• 关键词: Alzheimer' s Disease; Anatomy; Arousal; Automobile Driving; Award; Behavior; Behavioral; Brain; Brain Diseases; Cells; Cognition; Cognitive; Decision Making; Dimensions; Electrophysiology (science); Epilepsy; Equipment; Event; Fire - disasters; Florida; Foundations; Frequencies; Future; Generations; Glutamates; Goals; Hippocampus; Hispanic-serving Institution; International; Knowledge; Laboratories; Learning; Link; Medial; Mediating; Memory; Mental disorders; Mentors; Methodology; Monitor; Neurons; Odors; Optics; Pathway interactions; Performance; Periodicity; Phase; Physiologic pulse; Physiological; Play; Population; Positioning Attribute; Pre-Clinical Model; Prefrontal Cortex; Principal Investigator; Process; Program Development; Public Health; REM Sleep; Rattus; Research; Research Personnel; Resources; Reuniens Thalamic Nucleus; Rodent; Role; Running; Sampling; Schizophrenia; Scientist; Shapes; Site; Sleep; Symptoms; System; Technical Expertise; Temporal Lobe; Testing; Thalamic structure; Theta Rhythm; Time; Training; Underrepresented Students; Universities; career; episodic like memory; excitatory neuron; experimental study; frontal lobe; memory consolidation; nervous system disorder; neural; neurophysiology; non rapid eye movement; optogenetics; programs; role model; skills; success; theories; therapeutic target

PROJECT SUMMARY The primary goal of the present proposal is to explore the role of pathway-specific RE neurons in the synchronized activity of the prefrontal-hippocampal circuit (mPFC-HC) and memory related rhythms in wake (episodic-like sequence memory) and in sleep states (REM/NREM). To accomplish this, Aim1 will determine if and how excitation of RE neurons can drive memory related mPFC-HC coherent states. The first experiment will test a range of relevant frequencies in RE-pathway specific neurons to identify a stimulation capable of driving mPFC-HC coherent modes in freely behaving rats. Using a closed-loop optogenetic approach, the second experiment will stimulate RE neurons to induce mPFC-HC coherence during different endogenous coherence states to boost memory performance while rats perform in a nonspatial sequence memory task. As I transition to my independent career (R00), Aim2 will explore the role of pathway-specific RE neurons in driving theta and delta related sleep oscillations (REM/NREM) using a closed-loop setup. Two new technical skills will be acquired during the K99 training phase which include 1) learning to run a sophisticated rodent sequence memory task capable of testing multiple RE-dependent memory dimensions, and 2) implementing a cutting edge closed-loop optogenetic control system capable of detecting neurophysiological coherence modes between the hippocampus and medial prefrontal cortex in `real-time' to trigger RE optogenetic stimulations. My previous training in anatomy, optogenetics, multisite electrophysiological recordings, and my theoretical background on RE-related mnemonic processes and arousal provides me with the foundation and technical skills necessary to pursue these goals with this additional training. Florida International University, a research- intensive and Hispanic-serving institution, is the ideal place to complete my training because it offers all the resources (mentor, equipment, facilities, and professional development programs) necessary to carry out the proposed experiments and training plan. The mentoring team is composed of two well-established and highly successful scientists, who together are committed to my success and will adequately prepare me for a career as an independent research investigator. The K99 phase of this award would allow me to enter the independent stage of my career with the theoretical, technical, methodological, networking, and laboratory management skills necessary to answer scientific questions at the circuit and network level, establish my own laboratory, and independently pursue future scientific directions. As a MOSAIC awardee and future principal investigator, one of my goals is to become a role model and mentor to other underrepresented students and scientists, so that I can enhance diversity, equality, and inclusion in the biomedical field. Overall, this research will shed new light on the role of RE in driving network-wide memory states, while the training plan will equip me professionally to launch my independent career.

项目摘要 本提案的主要目标是探索通路特异性RE神经元在细胞凋亡中的作用。 清醒时额叶前-海马回路（mPFC-HC）的同步活动与记忆相关节律 （类似情节的序列记忆）和睡眠状态（REM/NREM）。为了实现这一点，Aim 1将确定是否 以及RE神经元的激发如何驱动记忆相关的mPFC-HC相干态。第一个实验 将测试RE通路特异性神经元中的一系列相关频率，以识别能够 在自由行为大鼠中驱动mPFC-HC相干模式。使用闭环光遗传学方法， 第二个实验将刺激RE神经元以诱导不同内源性期间的mPFC-HC相干性。 相干状态，以提高记忆性能，而大鼠在非空间序列记忆任务。正如我 过渡到我的独立职业生涯（R 00），Aim 2将探索路径特异性RE神经元在驾驶中的作用 θ和δ相关的睡眠振荡（REM/NREM）使用闭环设置。两项新技能将 在K99训练阶段获得，包括1）学习运行复杂的啮齿动物序列 能够测试多个依赖于RE的存储器维度的存储器任务，以及2）实现切割 可检测神经生理相干模式的边缘闭环光遗传学控制系统 在海马体和内侧前额叶皮层之间“实时地”触发RE光遗传学刺激。 我以前在解剖学，光遗传学，多点电生理记录方面的训练，以及我的理论 关于RE相关的记忆过程和唤醒的背景为我提供了基础和技术 通过这种额外的培训来实现这些目标所需的技能。佛罗里达国际大学，一项研究- 密集和西班牙裔服务机构，是完成我的培训的理想场所，因为它提供了所有的 资源（导师、设备、设施和专业发展计划）， 提出实验和培训计划。指导团队由两名知名且高度专业的 成功的科学家，他们一起致力于我的成功，并将充分准备我的职业生涯 作为一个独立的研究员。这个奖项的K99阶段将允许我进入 我的职业生涯的独立阶段与理论，技术，方法论，网络和实验室 必要的管理技能，以回答科学问题，在电路和网络的水平，建立我自己的 实验室，并独立追求未来的科学方向。作为MOSAIC获奖者和未来的校长 调查员，我的目标之一是成为其他代表性不足的学生的榜样和导师， 科学家，这样我就可以提高生物医学领域的多样性，平等性和包容性。 总的来说，这项研究将揭示RE在驱动网络范围内的记忆状态中的作用，而 培训计划将使我具备专业知识，开始我的独立职业生涯。