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

• 批准号: 10677962
• 负责人: Bibi Alika Sulaman
• 金额: $ 4.02万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/10677962
• 关键词: Affect; Anatomy; Animals; Arousal; Behavior; Binding; Brain; Brain region; Calcium; Cells; Communication; Computer Analysis; Data; Data Reporting; Dependence; Development; Disease; Dopamine; Electrophysiology (science); Environment; Event; Food; Head; Hippocampus; Image; Knowledge; Learning; Life Experience; Link; Memory; Memory impairment; Mental disorders; Michigan; Microscope; Molecular; Mus; Nature; Negative Valence; Neurons; Neurosciences; Pattern; Play; Population; Positive Valence; Post-Traumatic Stress Disorders; Probability; Process; REM Sleep; Research; Research Personnel; Resolution; Role; Sensory; Signal Transduction; Sleep; Stimulus; Substance Use Disorder; Synaptic plasticity; System; Testing; Time; Training; Universities; Ventral Tegmental Area; dopaminergic neuron; experience; experimental study; innovation; insight; long term memory; maladaptive behavior; member; memory consolidation; memory process; memory recall; non rapid eye movement; novel therapeutic intervention; novel therapeutics; optogenetics; skills; tool

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.

项目摘要/摘要 在所有生活经历中，显着的经历是最有可能的人。将经验存储到长期 术语记忆被认为取决于在睡眠期间发生的学习后整合过程。尽管 关于如何将空间和感官信息纳入记忆的知名度，这些机制通过 经验的哪些显着方面与内存的其他组成部分有关，仍然在很大程度上未知。一个 与编码显着性有关的中央神经元种群是腹侧换段区域多巴胺（VTADA） 神经元。 VTADA神经元编码，对于形成正价和负价是必要的 关联，并且在解剖和功能上与与记忆有关的大脑区域有联系 合并。先前的研究和我们的初步数据表明，睡眠期间的VTADA神经元活动是 依赖经验，但是睡眠期间VTADA神经元的激活在记忆中是否具有因果作用 合并，醒来的经历的特定组成部分，影响睡眠期间VTADA神经元活动 VTADA神经元活性与海马依赖性记忆巩固过程的整合 在很大程度上未知。我们假设睡眠期间VTADA神经元中的活动在联系中起着至关重要的作用 经验的显着方面与内存跟踪的其他方面。我们建议阐明决定因素， VTADA神经元中经验依赖性活动和重新激活事件的内容和时间顺序 睡眠（AIM 1），并在睡眠过程中询问VTADA神经元活动的功能 内存合并（AIM 2）。为了实现这些目标，我们开发了一种创新的方法 结合合奏级钙成像，电生理记录，光学遗传操作和 自由行为和沉睡的老鼠中的各种学习任务。我们的发现将提供基本的新见解 关于将多个大脑区域中编码的信息整合到连贯的多方面记忆中 在睡眠期间。此外，我们的研究可以促进新的治疗方法的发展 与多巴胺信号和失调的多巴胺信号和相关的各种精神疾病 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 当我发展成为独立研究人员时，通过全面而严格的培训。