Spatial cell-type enrichment predicts mouse brain connectivity

Cell Rep. 2023 Oct 31;42(10):113258. doi: 10.1016/j.celrep.2023.113258. Epub 2023 Oct 19.

Abstract

A fundamental neuroscience topic is the link between the brain's molecular, cellular, and cytoarchitectonic properties and structural connectivity. Recent studies relate inter-regional connectivity to gene expression, but the relationship to regional cell-type distributions remains understudied. Here, we utilize whole-brain mapping of neuronal and non-neuronal subtypes via the matrix inversion and subset selection algorithm to model inter-regional connectivity as a function of regional cell-type composition with machine learning. We deployed random forest algorithms for predicting connectivity from cell-type densities, demonstrating surprisingly strong prediction accuracy of cell types in general, and particular non-neuronal cells such as oligodendrocytes. We found evidence of a strong distance dependency in the cell connectivity relationship, with layer-specific excitatory neurons contributing the most for long-range connectivity, while vascular and astroglia were salient for short-range connections. Our results demonstrate a link between cell types and connectivity, providing a roadmap for examining this relationship in other species, including humans.

Keywords: CP: Cell biology; CP: Neuroscience; cell biology; connectivity; data science; machine learning; networks; neuroscience; transcriptomics.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Algorithms
  • Animals
  • Brain Mapping* / methods
  • Brain* / physiology
  • Humans
  • Mice
  • Neurons / physiology
  • Random Forest