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03.12.2020 20:15
Mapping neural circuits in the developing brain
How can one build neural networks that are more complex than anything we know to this day? Researchers at the Max Planck Institute for Brain Research in Frankfurt am Main have mapped the development of inhibitory neural circuits and report on several very precise construction principles for building neural networks. Their results make it possible to track changes in the neural network structure over time and to capture them in moments in which an individual grows and adapts to his environment.
Researchers are increasingly understanding the complexity of the neural networks in our brains and those of animals. But how can such precise and nested neural circuits be formed in the first place? Today we know how neurons are born, migrate to their place in the gray matter, how they grow and differentiate. But how and according to which rules do the billions of synapses, the sophisticated contact points, through which neurons communicate with each other and form the neuronal circuits, develop, often at highly precise points in the brain?
In the study published today in Science, a team led by Max Planck Director Moritz Helmstaedter analyzed a total of thirteen three-dimensional data sets from the cortex of mice in various stages of development: after birth, at times similar to those of babies, children, adolescents and young adults are comparable. They used methods from “connectomics” to map the neural circuits in the gray matter of the cerebral cortex, in which most of the synapses of the cerebrum are located. They focused on the synapses of a certain type of nerve cell called interneurons, which are known to inhibit the activity of other neurons in a highly specific way. The researchers were able to follow the development of the synaptic “partner choice” for these special types of nerve cells.
“Surprisingly, different types of interneurons followed very different time courses in their ‘partner choice’. Some interneurons networked with their synaptic partners in the earliest stages of the circuits examined (corresponding to the brains of babies), with a preference that is synaptic preference in circuits This happened when the first chemical synapses were formed in the gray matter of the cortex. Other interneurons showed strong improvements in target and partner selection, most likely caused by the removal of misplaced synapses, “explains Anjali Gour, PhD student in the department and lead author of this study.
Earlier studies had already found that synapses are not only newly formed during brain development, but that some existing synapses have to be destroyed again. The realization that synapse elimination (English: “pruning”) performs a precise and specific function for the formation of inhibitory circuits was a real surprise. The researchers also found that an important class of interneurons called chandelier neurons, believed to be fully established in early adolescence, had innervation much earlier and more systematically (Networking) their synaptic partner structures show as previously known.
These findings were possible even though the mapping of connectomes is a snapshot technique: Neural networks can be measured in biopsies of brain tissue, but cannot be traced over time in the same brain tissue. Rather, many mappings of samples from different brains must be performed. “The fact that we were nevertheless able to extract a clear development profile from this data shows the information density that is present in the connectomic data,” says Gour. “I didn’t think we would find such clear circuit patterns in developing brains,” she adds.
It is believed that developmental processes during the formation of neural networks and their possible disruption are essential contributors to some of the most important psychiatric diseases. Inhibitory circuits are a particular focus of research in the study of these functional disorders. Therefore, a precise and detailed understanding of the inhibitory circuits is a prerequisite for the specific analysis and for possible interventions in such disease states. “We hope to be able to map normal and disturbed network formation in cortical circuits much more precisely in order to understand possible changes in psychiatric illnesses and possibly to identify the phenotypes of connectopathies,” says Helmstaedter.
The researchers obtained the findings from this study through the use of “connectomic screening”, made possible by the meanwhile significantly higher throughput of the connectomic methods. “We expect this approach to be as widespread as genetic screening in the future: the study of the structure of neural networks under a wide range of normal and pathological circumstances to understand the changes and similarities found in mammalian brains “.
Scientific contact:
Prof. Dr. Moritz Helmstaedter
Director, Max Planck Institute for Brain Research
Frankfurt am Main
+49 69 850033 3001
[email protected]
Originalpublikation:
Anjali Gour, Kevin M. Boergens, Natalie Heike, Yunfeng Hua, Philip Laserstein, Kun Song, and Moritz Helmstaedter. Postnatal connectomic development of inhibition in mouse barrel cortex. Science, Online publication: December 3, 2020 DOI:http://science.sciencemag.org/lookup/doi/10.1126/science.abb4534. Cite as: Gour et al., Science 2020. DOI: 10.1126/science.abb4534
Further information:
https://youtu.be/tVdkPvDa1JM PR Video (c) Gour et al., Science 2020. DOI: 10.1126/science.abb4534
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