BRICseq Bridges Brain-wide Interregional Connectivity to Neural Activity and Gene Expression in Single Animals

Cell. 2020 Jul 9;182(1):177-188.e27. doi: 10.1016/j.cell.2020.05.029. Epub 2020 Jul 2.

Abstract

Comprehensive analysis of neuronal networks requires brain-wide measurement of connectivity, activity, and gene expression. Although high-throughput methods are available for mapping brain-wide activity and transcriptomes, comparable methods for mapping region-to-region connectivity remain slow and expensive because they require averaging across hundreds of brains. Here we describe BRICseq (brain-wide individual animal connectome sequencing), which leverages DNA barcoding and sequencing to map connectivity from single individuals in a few weeks and at low cost. Applying BRICseq to the mouse neocortex, we find that region-to-region connectivity provides a simple bridge relating transcriptome to activity: the spatial expression patterns of a few genes predict region-to-region connectivity, and connectivity predicts activity correlations. We also exploited BRICseq to map the mutant BTBR mouse brain, which lacks a corpus callosum, and recapitulated its known connectopathies. BRICseq allows individual laboratories to compare how age, sex, environment, genetics, and species affect neuronal wiring and to integrate these with functional activity and gene expression.

Keywords: BRICseq; MAPseq; connectome; high-throughput sequencing; mesoscale.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Brain Mapping
  • Connectome*
  • Decision Making
  • Gene Expression Regulation*
  • Male
  • Mice, Inbred C57BL
  • Mice, Neurologic Mutants
  • Nerve Net / physiology*
  • Neurons / physiology*
  • Reproducibility of Results
  • Sequence Analysis, DNA*
  • Task Performance and Analysis