Correlated Gene Expression and Anatomical Communication Support Synchronized Brain Activity in the Mouse Functional Connectome

Brian D Mills, David S Grayson, Anandakumar Shunmugavel, Oscar Miranda-Dominguez, Eric Feczko, Eric Earl, Kim A Neve, Damien A Fair

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Cognition and behavior depend on synchronized intrinsic brain activity that is organized into functional networks across the brain. Research has investigated how anatomical connectivity both shapes and is shaped by these networks, but not how anatomical connectivity interacts with intra-areal molecular properties to drive functional connectivity. Here, we present a novel linear model to explain functional connectivity by integrating systematically obtained measurements of axonal connectivity, gene expression, and resting-state functional connectivity MRI in the mouse brain. The model suggests that functional connectivity arises from both anatomical links and inter-areal similarities in gene expression. By estimating these effects, we identify anatomical modules in which correlated gene expression and anatomical connectivity support functional connectivity. Along with providing evidence that not all genes equally contribute to functional connectivity, this research establishes new insights regarding the biological underpinnings of coordinated brain activity measured by BOLD fMRI.SIGNIFICANCE STATEMENT Efforts at characterizing the functional connectome with fMRI have risen exponentially over the last decade. Yet despite this rise, the biological underpinnings of these functional measurements are still primarily unknown. The current report begins to fill this void by investigating the molecular underpinnings of the functional connectome through an integration of systematically obtained structural information and gene expression data throughout the rodent brain. We find that both white matter connectivity and similarity in regional gene expression relate to resting-state functional connectivity. The current report furthers our understanding of the biological underpinnings of the functional connectome and provides a linear model that can be used to streamline preclinical animal studies of disease.

Original languageEnglish (US)
Pages (from-to)5774-5787
Number of pages14
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Volume38
Issue number25
DOIs
StatePublished - Jun 20 2018
Externally publishedYes

Bibliographical note

Copyright © 2018 the authors 0270-6474/18/385774-14$15.00/0.

Keywords

  • Animals
  • Brain/physiology
  • Connectome
  • Gene Expression/physiology
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Models, Neurological
  • Nerve Net/physiology

PubMed: MeSH publication types

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

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