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

项目总结 本研究的主要目的是探讨通路特异性RE神经元在中枢神经系统中的作用。 觉醒时前额-海马区(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，Aim1将确定 以及RE神经元的兴奋如何驱动记忆相关的mPFC-HC相干态。第一个实验 将测试RE通路特定神经元的一系列相关频率，以确定能够 在自由行为大鼠中驱动mPFC-HC相干模式。使用闭合环光遗传方法， 第二个实验将刺激RE神经元在不同的内源性刺激下诱导mPFC-HC的一致性 当大鼠在非空间序列记忆任务中执行任务时，一致性状态可以提高记忆性能。就像我 过渡到我的独立职业生涯(R00)，AIM2将探索特定路径的RE神经元在驾驶中的作用 使用闭环设置的Theta和Delta相关睡眠振荡(REM/NREM)。两项新的技术技能将 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RE依赖的记忆维度的记忆任务，以及2)实现切割 一种可检测神经生理相干模式的边缘闭环光遗传控制系统 在海马体和内侧前额叶皮质之间的“实时”，以触发RE光遗传刺激。 我之前在解剖学、光遗传学、多部位电生理记录和我的理论方面的培训 RE相关助记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- 是完成我培训的理想地方，因为它提供所有 执行项目所需的资源(导师、设备、设施和职业发展计划) 提出了实验和培训计划。指导团队由两位久负盛名的资深人士和 成功的科学家，他们一起致力于我的成功，并为我的职业生涯做好充分的准备 作为一名独立研究调查员。这个奖项的K99阶段将允许我进入 我职业生涯的独立阶段，在理论、技术、方法、网络和实验室方面 在电路和网络层面回答科学问题所需的管理技能，建立自己的 实验室，并独立追求未来的科学方向。作为马赛克奖获得者和未来的校长 调查员，我的目标之一是成为其他代表不足的学生的榜样和导师 科学家们，这样我就可以加强生物医学领域的多样性、平等和包容性。 总体而言，这项研究将为RE在驱动网络范围内的记忆状态中的作用提供新的线索，而 培训计划将为我开始独立的职业生涯做好专业准备。

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.