Title: Functionally Distinct Neuronal Ensembles within the Memory Engram
Author: Xiaochen Sun, Max J. Bernstein, Meizhen Meng, Siyuan Rao, Andreas T. Srensen, Li Yao, Xiaohui Zhang, Polina O. Anikeeva, Yingxi Lin
Abstract: 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 memoryengrams, i.e., if separate neuronal subpopulations encode distinct aspects of thememory and drive memory expression differently. Here, we show that contextual fearmemory 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 excitatorysynaptic inputs from the medial entorhinal cortex, which we find itself also mediatesgeneralization. The Npas4-dependent ensemble promotes memory discrimination and receives enhanced inhibitorydrive from local cholecystokinin-expressing interneurons, the activity of which isrequired for discrimination. Our study provides causal evidence for functional heterogeneitywithin the memory engram and reveals synaptic and circuit mechanisms used by eachensemble to regulate the memory discrimination-generalization balance.