Deciphering the role of VTA dopaminergic signaling in memory consolidation during sleep

解读 VTA 多巴胺能信号在睡眠期间记忆巩固中的作用

基本信息

  • 批准号:
    10677962
  • 负责人:
  • 金额:
    $ 4.02万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-05-01 至 2026-04-30
  • 项目状态:
    未结题

项目摘要

Project Summary/Abstract Of all life experiences, salient ones are the likeliest to be remembered. The storage of experiences into long- term memory is thought to depend on post-learning consolidation processes occurring during sleep. While much is known on how spatial and sensory information is incorporated into memory, the mechanisms through which salient aspects of experiences are linked to other components of a memory are still largely unknown. A central neuronal population implicated in encoding salience is the ventral tegmental area dopamine (VTADA) neurons. VTADA neurons encode, and are necessary for the formation of, both positive and negative valence associations, and are anatomically and functionally connected with brain regions implicated in memory consolidation. Prior research and our preliminary data suggest that VTADA neuronal activity during sleep is experience-dependent, yet whether the activation of VTADA neurons during sleep has a causal role in memory consolidation, the specific components of waking experiences that affect VTADA neuronal activity during sleep and the integration of VTADA neuronal activity with hippocampal-dependent memory consolidation processes are largely unknown. We hypothesize that activity in VTADA neurons during sleep plays a critical role in linking salient aspects of experiences to other aspects of a memory trace. We propose to elucidate the determinants, contents and time-course of experience-dependent activity and reactivation events in VTADA neurons during sleep (Aim 1) and causally interrogate the function of VTADA neuronal activity during sleep in processes of memory consolidation (Aim 2). To achieve these aims, we have developed an innovative approach that combines ensemble-level calcium imaging, electrophysiological recordings, optogenetic manipulations and various learning tasks in freely behaving and sleeping mice. Our findings will provide fundamental new insight regarding the integration of information encoded in multiple brain regions into coherent multifaceted memories during sleep. Moreover, our research could promote the development of new therapeutic approaches for various psychiatric disorders that are associated with a combination of dysregulated dopamine signaling and impaired memory. The training plan we have developed, which draws on the skills and expertise of my various sponsors, as well as the strengths of the research environment at the University of Michigan, will provide me with comprehensive and rigorous training as I develop into an independent researcher.
项目总结/摘要 在所有的生活经历中,突出的经历最有可能被记住。把经验储存在长期的- 术语记忆被认为依赖于在睡眠期间发生的学习后巩固过程。而 关于空间和感觉信息是如何被纳入记忆的, 经验的哪些突出方面与记忆的其他组成部分相关联,在很大程度上仍然是未知的。一 涉及编码显著性的中枢神经元群是腹侧被盖区多巴胺(VTADA) 神经元腹侧被盖区神经元编码阳性和阴性效价,并且是形成阳性和阴性效价所必需的 关联,并且在解剖学和功能上与涉及记忆的大脑区域相关 合并。先前的研究和我们的初步数据表明,VTADA神经元在睡眠期间的活动, 经验依赖性,但是否VTADA神经元的激活在睡眠中有一个因果关系的作用,记忆 巩固,在睡眠期间影响VTADA神经元活动的清醒经历的特定成分 以及VTADA神经元活动与海马依赖性记忆巩固过程的整合 大部分都是未知的。我们假设睡眠期间腹侧被盖区神经元的活动在连接 经验的突出方面与记忆痕迹的其他方面。我们建议阐明决定因素, VTADA神经元经验依赖性活动和再激活事件的内容和时程 睡眠(目的1)和因果询问的功能,VTADA神经元活动在睡眠过程中, 记忆巩固(目标2)。为了实现这些目标,我们开发了一种创新方法, 结合了整体水平的钙成像,电生理记录,光遗传学操作和 在自由行为和睡眠的小鼠中进行各种学习任务。我们的发现将为我们的研究提供 关于将多个大脑区域编码的信息整合成连贯的多面记忆, 在睡眠中。此外,我们的研究可以促进新的治疗方法的发展, 与多巴胺信号传导失调和 记忆力受损我们制定的培训计划借鉴了我的各种技能和专业知识, 赞助商,以及密歇根大学的研究环境的优势,将为我提供 经过全面而严格的训练,我将成为一名独立的研究人员。

项目成果

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