Xingyu Ding, Sean Froudist-Walsh, Jorge Jaramillo, Junjie Jiang, Xiao-Jing Wang

Cell type-specific connectome predicts distributed working memory activity in the mouse brain

  • General Immunology and Microbiology
  • General Biochemistry, Genetics and Molecular Biology
  • General Medicine
  • General Neuroscience
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Recent advances in connectome and neurophysiology make it possible to probe whole-brain mechanisms of cognition and behavior. We developed a large-scale model of the mouse multiregional brain for a cardinal cognitive function called working memory, the brain's ability to internally hold and process information without sensory input. The model is built on mesoscopic connectome data for inter-areal cortical connections and endowed with a macroscopic gradient of measured parvalbumin-expressing interneuron density. We found that working memory coding is distributed yet exhibits modularity; the spatial pattern of mnemonic representation is determined by long-range cell type-specific targeting and density of cell classes. Cell type-specific graph measures predict the activity patterns and a core subnetwork for memory maintenance. The model shows numerous self-sustained internal states (each engaging a distinct subset of areas). This work provides a framework to interpret large-scale recordings of brain activity during cognition, while highlighting the need for cell type-specific connectomics.

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