Large-scale topology and the default mode network in the mouse connectome

Resting-state functional connectivity MRI (rs-fcMRI) can be reliably performed in mice, producing high-resolution whole-brain images. The functional connections strongly align with the brain's structural wiring, as mapped by anterograde tracer studies. Large-scale network properties previously seen only in primates also exist in rodents, though with some differences. A potential default mode network (DMN)—a system important for social cognition and disrupted in many disorders—was identified in the mouse brain both structurally and functionally. These findings validate mouse rs-fcMRI as a translational bridge, allowing stronger links between cellular and molecular manipulations in mice and human brain conditions.

Study at a glance

Abstract

Noninvasive functional imaging holds great promise for serving as a translational bridge between human and animal models of various neurological and psychiatric disorders. However, despite a depth of knowledge of the cellular and molecular underpinnings of atypical processes in mouse models, little is known about the large-scale functional architecture measured by functional brain imaging, limiting translation to human conditions. Here, we provide a robust processing pipeline to generate high-resolution, whole-brain resting-state functional connectivity MRI (rs-fcMRI) images in the mouse. Using a mesoscale structural connectome (i.e., an anterograde tracer mapping of axonal projections across the mouse CNS), we show that rs-fcMRI in the mouse has strong structural underpinnings, validating our procedures. We next directly show that large-scale network properties previously identified in primates are present in rodents, although they differ in several ways. Last, we examine the existence of the so-called default mode network (DMN)--a distributed functional brain system identified in primates as being highly important for social cognition and overall brain function and atypically functionally connected across a multitude of disorders. We show the presence of a potential DMN in the mouse brain both structurally and functionally. Together, these studies confirm the presence of basic network properties and functional networks of high translational importance in structural and functional systems in the mouse brain. This work clears the way for an important bridge measurement between human and rodent models, enabling us to make stronger conclusions about how regionally specific cellular and molecular manipulations in mice relate back to humans.