How does activity of CA3 engram neurons affect CA1 spatial codes?

CA3 印迹神经元的活动如何影响 CA1 空间编码？

• 批准号: 456352444
• 负责人: Dr. Alessio Attardo
• 金额: --
• 依托单位: Bernstein Center Freiburg
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/456352444?language=en
• 关键词: How; does; activity; CA3; engram

Hippocampal pyramidal neurons can encode the spatial location of an animal through localized firing patterns, or place cells. Studies on humans and animals have shown a critical role for the hippocampus in spatial and episodic memory. It is largely thought that long-term spatial memory arises from ensembles of cells that retain their spatial coding properties over time periods relevant to long-term memory. Recently, however, a surprising level of instability has been demonstrated in the hippocampus. In fact, hippocampal spatial representations have both dynamic and stable facets. In rodents, there is day-to-day turnover in the set of hippocampal cells representing environments, which might help distinguish the representations of the different visits. However, individual CA1 neural place fields can exhibit long-term stability. Overall, the mechanisms supporting turnover versus stability of hippocampal representations are completely unknown.Ensembles of neurons undergoing coordinated activity-dependent plasticity not only represent experience but are also functional for learning and memory recall, thus they are largely believed to be cellular memory engrams. The activity of engram neurons has a key role in systems memory consolidation. As hippocampal representations are postulated to support memory formation and consolidation, engram neurons should also be important for the dynamics of these representations. Still, this issue is largely unexplored mostly owing to technical difficulties. In this project we propose to combine the complementary expertise of our laboratories to investigate the systems mechanisms that lead to turnover and specificity of representations in hippocampal CA1. Specifically, we will investigate how activity of CA3 engram neurons affects turnover, specificity and directionality of CA1 spatial representations. To achieve these aims we will take advantage of our laboratories’ cutting-edge technologies and analysis frameworks. We will combine Wide Field Head Mounted microscopes - to record neuronal activity in the CA1 of mice as they explore different environments - with optogenetics - to control the activity of CA3 engram neurons – and used advanced analysis tools to investigate the effects of forced re-activation of CA3 engram neurons on activity patters of CA1 neurons.

海马锥体神经元可以通过局部放电模式或定位细胞编码动物的空间位置。对人类和动物的研究表明，海马体在空间和情景记忆中起着关键作用。人们普遍认为，长期空间记忆来自于细胞的集合，这些细胞在与长期记忆相关的时间段内保持其空间编码特性。然而，最近，海马体的不稳定程度令人惊讶。事实上，海马的空间表征既有动态的，也有稳定的。在啮齿动物中，代表环境的海马细胞组中存在日常周转，这可能有助于区分不同访问的表征。然而，单个CA 1神经位置场可以表现出长期稳定性。总体而言，支持海马表征的翻转与稳定性的机制是完全未知的。经历协调的活动依赖性可塑性的神经元集合不仅代表经验，而且还具有学习和记忆回忆的功能，因此它们在很大程度上被认为是细胞记忆痕迹。记忆印迹神经元的活动在系统记忆巩固中起着关键作用。由于海马表征被假定为支持记忆的形成和巩固，因此记忆痕迹神经元对于这些表征的动力学也应该是重要的。然而，这个问题在很大程度上还没有得到探讨，主要是由于技术上的困难。在这个项目中，我们建议联合收割机的互补专业知识，我们的实验室调查的系统机制，导致营业额和特异性的代表在海马CA 1区。具体来说，我们将研究如何活动的CA 3记忆痕迹神经元影响营业额，特异性和方向性的CA 1空间表示。为了实现这些目标，我们将利用我们实验室的尖端技术和分析框架。我们将结合联合收割机宽视场头戴式显微镜-记录神经元的活动在小鼠的CA 1，因为他们探索不同的环境-与光遗传学-控制CA 3记忆痕迹神经元的活动-并使用先进的分析工具，以研究强制重新激活的CA 3记忆痕迹神经元对CA 1神经元的活动模式的影响。