Connectomics Used to Map Development of Inhibitory Neuronal Circuitry

Researchers at the Max Planck Institute for Brain Research have mapped the development of inhibitory neuronal circuitry and in the process discovered distinct circuit formation principles. Their findings were published in Science today.

The team analyzed a total of thirteen 3-dimensional datasets from the cortex of mice during different stages of development: after birth, at time points comparable to baby, child, teenager and young adult. They used connectomics methodology to map out the neuronal circuitry found in the gray matter of the cerebral cortex, where most of the cerebral synapses are placed. By focusing on interneurons, which are known to inhibit the activity of other neurons in highly specific ways, they were able to track the development of synaptic partner choice for these particular types of nerve cells.

"Surprisingly, different types of interneurons followed very different time courses to establish their favorite synaptic partners. Some were able to innervate their synaptic targets with adult-like preference already in the first investigated circuit stages that correspond to baby brains. This happened immediately when the first chemical synapses were formed in the cortical gray matter. Others showed steep improvements of target choice, which were most likely caused by removal of incorrectly placed synapses," explains Anjali Gour, first author of this study.

The developmental processes of neuronal network formation and their possible disruption are thought to be major contributors to some of the main psychiatric disorders, and a particular focus of research has identified a contribution of inhibitory circuits to these dysfunctions. Hence, a precise and detailed understanding of inhibitory circuit is a prerequisite for targeted analysis and possible interference in such disease conditions. "We hope to be able to map much more precisely the normal and disrupted network formation in cortical circuits for understanding possible alterations in psychiatric disease, and possibly identify the phenotypes of connectopathies," says senior author Moritz Helmstaedter.