Chemogenetic manipulation and transformation of the motor memory network

运动记忆网络的化学遗传学操纵和转化

• 批准号: RGPIN-2021-02569
• 负责人: Sekeres, Melanie
• 金额: $ 2.4万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=741918
• 关键词: Chemogenetic; manipulation; transformation; motor; memory

The development of a new skill like riding a bike is viewed as a motor task, yet the initial acquisition of that skill is linked to the unique experience of the first time you rode a bike. Dissociating the episodic memory experience of the event from the motor memory component of the experience is difficult. Despite not explicitly recalling the episodic components of that unique first bike riding experience each time you get on a bike, the implicit motor memory supports performance of the skill. Like the episodic memory for the event, the motor memory for the skill changes over time (becomes more familiar through repeated performance), and this transformed version of the motor memory is accompanied by a reorganization of neural activity. The prolonged process of systems consolidation and neural network reorganization of episodic memory has been well characterized in both humans and rodents, but the factors mediating systems consolidation and network reorganization of the motor memory network remain unclear. My research program aims to (objective 1) identify how motor memory networks reorganize over time, and (objective 2) determine how silencing key nodes of the episodic memory network (hippocampus, medial prefrontal cortex) propagates to impact activity within the motor memory network (motor cortex, striatum, cerebellum) at recent and remote timepoints. Critically, by varying the age of the memory (1 day or 1 month old), the frequency of training (2 training sessions of 20 training sessions), and the training context (familiar or novel contexts), we can dissociate the contributions of time, practice, and context in mediating motor memory systems consolidation and memory transformation observed across the brain. The necessity of key nodes of the episodic memory network in motor memory consolidation and retrieval will be determined by chemogenetically silencing the hippocampus or medial prefrontal cortex using inhibitory DREADDs in mice, then identifying changes in activation of the motor memory network in the absence of hippocampus or medial prefrontal cortical input during motor task performance. Demonstrating analogous patterns of systems consolidation and identifying how disruption of key nodes of the network alter activity will bolster, or challenge, the current understanding of memory reorganizational processes in the brain. If a consistent pattern of reorganization is observed across declarative (episodic) and non-declarative (motor) memory, this may identify memory transformation as a fundamental process of memory consolidation, and will highlight the importance of investigating other forms of non-declarative memory network reorganization in the brain.

像骑自行车这样的新技能的发展被视为一项运动任务，但这项技能的最初获得与你第一次骑自行车的独特体验有关。很难将事件的情节记忆体验从体验的运动记忆成分中分离出来。尽管你每次骑自行车时都不会明确地回忆起第一次骑车经历中的插曲，但内隐的运动记忆支持这项技能的表现。就像对事件的情节记忆一样，对技能的运动记忆随着时间的推移而变化(通过重复表演变得更加熟悉)，这种运动记忆的转换版本伴随着神经活动的重组。在人类和啮齿动物中，情节记忆的系统巩固和神经网络重组的漫长过程已经被很好地描述，但调节运动记忆网络的系统巩固和网络重组的因素仍然不清楚。我的研究计划旨在(目标1)确定运动记忆网络如何随着时间的推移而重组，以及(目标2)确定静默情景记忆网络(海马体、内侧前额叶皮质)的关键节点如何传播，以影响运动记忆网络(运动皮质、纹状体、小脑)在最近和远程时间点内的活动。重要的是，通过改变记忆的年龄(1天或1个月大)、训练的频率(20个训练课程的2个训练课程)和训练环境(熟悉的或新的环境)，我们可以分离出时间、实践和环境在调节整个大脑中观察到的运动记忆系统的巩固和记忆转换中的作用。情景记忆网络的关键节点在运动记忆巩固和提取中的必要性将通过使用抑制性DREADDS通过化学遗传学方法沉默小鼠的海马体或内侧前额叶皮质来确定，然后识别在运动任务执行过程中没有海马体或内侧前额叶皮质输入的情况下运动记忆网络激活的变化。展示系统整合的类似模式，并确定网络关键节点的中断如何改变活动将如何支持或挑战目前对大脑中记忆重组过程的理解。如果在陈述性(情节)和非陈述性(运动)记忆中观察到一致的重组模式，这可能确定记忆转换是记忆巩固的基本过程，并将突出研究大脑中其他形式的非陈述性记忆网络重组的重要性。