Mapping mouse brain by Mouse Connectome Project reveals how different brain regions communicate
(by Haohao Wu, )

Without understanding how brain works as a whole, studying its separated parts or circuits is an open-ended quest. Last year, the Brain Activity Map project and Blue Brain Project announced by the US President Obama and European Commission aim at having a comprehensive understanding of human brain by mapping neural activity or simulation of whole brain. In fact, scientists have been already working on mapping the mouse brain for years. Recently, researchers from the University of Southern California published their careful reconstruction of neuronal connections in mouse cerebral cortex from high resolution images of neuronal pathways. The raw data is freely online at the Mouse Connectome Project.

Graphic abstract of the Mouse Connectome Project.

Fig. 1: Graphic abstract of the Mouse Connectome Project.
(Image credit: Brian Zingg et al./Cell)

In this study, the researchers used double coinjection tract tracing, highlighting four pathways with different colors in one mouse brain. Each of the two coinjection sites consists of one anterograde and one retrograde tracer. Anterograde tracers label axons arising from the coinjection sites and their terminals in targeted regions while retrograde tracer label upstream neurons that innervate the coinjection sites. In other words, for eachcoinjection site, two fluorescent tracers reveal what areas this site projects to and what areas project to this site respectively. A total of 240 intracortical connections were manually reconstructed from over 600 labeled neuronal pathways placed across the entire mouse cerebral cortex to build up a comprehensive map of neuronal connections in mouse cerebral cortex.

Fluorescent labeled axons (green) and neurons (pink).

Fig. 2: Fluorescent labeled axons (green) and neurons (pink) after tracers injected in the controlateral side of cortex. This large image is the closeup of the boxed area in the whole brain section in lower right corner.
(Image credit: Brian Zingg et al./Cell)

The researchers further generated connectivity matrices to better analyze the intracortical connectivity and subnetwork clusters. Both the cortical map and connectivity matrices revealed that the mouse cerebral cortex is not a single interconnected neural network as thought before but indeed organized into eight distinct subnetworks: four somatic sensorimotor, two medial and two lateral subnetworks. Functional significance of these subnetworks were identified, e.g. four somatic sensorimotor are devoted to movements in the face, upper limbs, lower limbs and trunk, and whiskers respectively.Interestingly, these submetworks display unique topologies, probably also indicating different mechanisms of information processing for each.What’s more, the researchers observed that several sites potentially serve as connections of different subnetworks throughout the limbic loop surrounding the entire cerebral cortex.

In past years, the neuronal connections in mouse cerebral cortex have been largely studied, however, Mouse Connectome Project has its notable value because the data is collected and analyzed in a homogenous fashion rather than previous patchworks. The open source data online is aninvaluabletool for researchers to study their regions of interest. Moreover, some brain disorders, e.g. Alzheimer's disease, may involve malfunctioning networks, therefore, a comprehensive map of brain connections will largely inform not only the studies of normal brain function but also the studies of brain diseases. Given the similarity between mammalian brains, knowledge of mouse brain could be potentially translated to the understanding of human brain and contribute to the mega brain projects such as the Brain Activity Map Project and Blue Brain Project.

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Zingg, Brian, Houri Hintiryan, Lin Gou, Monica Y. Song, Maxwell Bay, Michael S. Bienkowski, Nicholas N. Foster et al. "Neural Networks of the Mouse Neocortex." Cell 156, no. 5 (2014): 1096-1111.