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Hippocampal neurons with stable excitatory connectivity become part of neuronal representations
PLOS Biology ( IF 9.8 ) Pub Date : 2020-11-03 , DOI: 10.1371/journal.pbio.3000928
Tim P. Castello-Waldow , Ghabiba Weston , Alessandro F. Ulivi , Alireza Chenani , Yonatan Loewenstein , Alon Chen , Alessio Attardo

Experiences are represented in the brain by patterns of neuronal activity. Ensembles of neurons representing experience undergo activity-dependent plasticity and are important for learning and recall. They are thus considered cellular engrams of memory. Yet, the cellular events that bias neurons to become part of a neuronal representation are largely unknown. In rodents, turnover of structural connectivity has been proposed to underlie the turnover of neuronal representations and also to be a cellular mechanism defining the time duration for which memories are stored in the hippocampus. If these hypotheses are true, structural dynamics of connectivity should be involved in the formation of neuronal representations and concurrently important for learning and recall. To tackle these questions, we used deep-brain 2-photon (2P) time-lapse imaging in transgenic mice in which neurons expressing the Immediate Early Gene (IEG) Arc (activity-regulated cytoskeleton-associated protein) could be permanently labeled during a specific time window. This enabled us to investigate the dynamics of excitatory synaptic connectivity—using dendritic spines as proxies—of hippocampal CA1 (cornu ammonis 1) pyramidal neurons (PNs) becoming part of neuronal representations exploiting Arc as an indicator of being part of neuronal representations. We discovered that neurons that will prospectively express Arc have slower turnover of synaptic connectivity, thus suggesting that synaptic stability prior to experience can bias neurons to become part of representations or possibly engrams. We also found a negative correlation between stability of structural synaptic connectivity and the ability to recall features of a hippocampal-dependent memory, which suggests that faster structural turnover in hippocampal CA1 might be functional for memory.



中文翻译:

具有稳定的兴奋性连接性的海马神经元成为神经元表征的一部分

经验在大脑中以神经元活动的方式表示。代表经验的神经元集合经历活动依赖的可塑性,对于学习和记忆很重要。因此,它们被认为是记忆的细胞标记。然而,使神经元偏向成为神经元表示的一部分的细胞事件在很大程度上是未知的。在啮齿动物中,已经提出了结构连通性的转换是神经元表征转换的基础,并且也是定义记忆存储在海马中的持续时间的细胞机制。如果这些假设是正确的,则连接性的结构动力学应参与神经元表示的形成,并且对学习和回忆起重要作用。为了解决这些问题,电弧(活性调节的细胞骨架相关蛋白)可以在特定时间范围内永久标记。这使我们能够研究以树突棘为代表的海马CA1(角u 1)锥体神经元(PNs)成为神经元表征的一部分的兴奋性突触连通性的动力学,利用Arc作为指示剂是神经元表征的一部分。我们发现,预期将表达弧的神经元具有突触连接性的转换较慢,因此表明在经历之前,突触稳定性会使神经元偏向成为表征或可能的信息的一部分。我们还发现结构突触连接的稳定性和召回海马依赖性记忆特征的能力之间存在负相关关系,这表明海马CA1中更快的结构更新可能对记忆起作用。

更新日期:2020-11-04
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