具有稳定兴奋性连接的海马神经元成为神经元表示的一部分。
Hippocampal neurons with stable excitatory connectivity become part of neuronal representations.
机构信息
Max Planck Institute of Psychiatry, Munich, Germany.
Graduate School of Systemic Neurosciences Ludwig-Maximilians-Universität, Munich, Germany.
出版信息
PLoS Biol. 2020 Nov 3;18(11):e3000928. doi: 10.1371/journal.pbio.3000928. eCollection 2020 Nov.
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.
经验是由神经元活动模式在大脑中表现出来的。代表经验的神经元集合经历了活动依赖性可塑性,这对于学习和回忆很重要。因此,它们被认为是记忆的细胞内印记。然而,使神经元偏向成为神经元表示一部分的细胞事件在很大程度上是未知的。在啮齿动物中,结构连接的周转率被提出是神经元表示的周转率的基础,也是定义海马体中记忆存储时间的细胞机制。如果这些假设是正确的,那么连接的结构动力学应该参与神经元表示的形成,同时对学习和回忆很重要。为了解决这些问题,我们使用了转基因小鼠的深部脑 2 光子(2P)延时成像,在该成像中,表达即时早期基因(IEG)Arc(活性调节细胞骨架相关蛋白)的神经元可以在特定时间窗口内永久标记。这使我们能够研究兴奋性突触连接的动态-使用树突棘作为海马 CA1(角状回 1)锥体神经元(PN)成为神经元表示一部分的代理-利用 Arc 作为成为神经元表示一部分的指标。我们发现,前瞻性表达 Arc 的神经元具有较慢的突触连接周转率,这表明在经历之前的突触稳定性可以使神经元偏向于成为表示或可能是印记的一部分。我们还发现结构突触连接稳定性与回忆海马依赖性记忆特征的能力之间存在负相关,这表明海马 CA1 中更快的结构周转率可能对记忆具有功能性。