Functionally Distinct Neuronal Ensembles within the Memory Engram.,Cell

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Functionally Distinct Neuronal Ensembles within the Memory Engram.
Cell ( IF 45.5 ) Pub Date : 2020-03-17 , DOI: 10.1016/j.cell.2020.02.055
Xiaochen Sun ₁ , Max J Bernstein ₂ , Meizhen Meng ₂ , Siyuan Rao ₃ , Andreas T Sørensen ₂ , Li Yao ₄ , Xiaohui Zhang ₄ , Polina O Anikeeva ₅ , Yingxi Lin ₆

Affiliation

McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Molecular and Cellular Neuroscience Graduate Program, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
State Key Laboratory of Cognitive Neuroscience & Learning and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China.
McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Memories are believed to be encoded by sparse ensembles of neurons in the brain. However, it remains unclear whether there is functional heterogeneity within individual memory engrams, i.e., if separate neuronal subpopulations encode distinct aspects of the memory and drive memory expression differently. Here, we show that contextual fear memory engrams in the mouse dentate gyrus contain functionally distinct neuronal ensembles, genetically defined by the Fos- or Npas4-dependent transcriptional pathways. The Fos-dependent ensemble promotes memory generalization and receives enhanced excitatory synaptic inputs from the medial entorhinal cortex, which we find itself also mediates generalization. The Npas4-dependent ensemble promotes memory discrimination and receives enhanced inhibitory drive from local cholecystokinin-expressing interneurons, the activity of which is required for discrimination. Our study provides causal evidence for functional heterogeneity within the memory engram and reveals synaptic and circuit mechanisms used by each ensemble to regulate the memory discrimination-generalization balance.

中文翻译：

记忆印迹内功能独特的神经元集合。

人们相信记忆是由大脑中稀疏的神经元群编码的。然而，目前尚不清楚个体记忆印迹内是否存在功能异质性，即不同的神经元亚群是否编码记忆的不同方面并以不同的方式驱动记忆表达。在这里，我们发现小鼠齿状回中的情境恐惧记忆印迹包含功能不同的神经元群，这些神经元群在基因上由 Fos 或 Npas4 依赖的转录途径定义。Fos 依赖性整体促进记忆泛化，并从内侧内嗅皮层接收增强的兴奋性突触输入，我们发现它本身也介导泛化。Npas4 依赖性整体促进记忆辨别，并从局部表达胆囊收缩素的中间神经元接收增强的抑制驱动，其活动是辨别所需的。我们的研究为记忆印迹内的功能异质性提供了因果证据，并揭示了每个整体用于调节记忆辨别泛化平衡的突触和回路机制。

更新日期：2020-04-20

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