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New Embryonic Brain Circuit Discovered

Using a new approach for studying live embryonic mouse brains at single-cell resolution, researchers have identified an active multi-layer circuit that forms in the cortex during an unexpectedly early stage of development.
Perturbing the circuit genetically led to changes similar to those seen in the brains of people with autism. The findings are reported today in Cell by a team based at the Institute of Molecular and Clinical Ophthalmology Basel.
“Understanding the detailed development of cell types and circuits in the cortex can provide important insights into autism and other neurodevelopmental diseases,” says Botond Roska, Director at IOB and the paper’s corresponding author. “This is what our findings confirm.”
Autism has long been associated with faulty circuits in the cortex, which is the part of the brain that governs sensory perception, cognition, and other high-order functions. Most of the cortex is composed of excitatory cells called pyramidal neurons.
The IOB team wanted to study when and how these neurons assemble into the first active circuits in the cortex, but that posed a difficult challenge. Pyramidal neurons measure only a tenth of the width of a human hair, and any movement during experimental procedures might lead to inaccurate recordings of activity.
To keep the neurons stable for research, the team devised a surgical solution: Embryos were secured inside of agar-filled 3D holding devices within the mother’s abdominal cavity, so that normal embryonic blood flow and temperature could be maintained.
The prevailing view is that the cortex develops in an “inside out fashion”, with the deepest of its six layers appearing first. Seen this way, pyramidal neurons were thought to slowly become active as they migrate to their final locations in the cortex and form connections with each other.
But during the research, “we actually detected a very different activity pattern,” says Arjun Bharioke, a systems neuroscientist in IOB’s Central Visual Circuits Group, and one of the paper’s two lead authors.

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