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New embryonic brain circuit discovered

Pyramidal neurons in normal mice and mice with autism-like symptoms.
Layer 5 pyramidal neurons in normal mice (left) compared with mice with autism gene knocked-out (right), showing a patch of disorganized cortex. (Microscopic image: IOB)

Researchers have identified a new brain circuit in mouse embryos that develops at an unexpectedly early stage. Their findings may provide new insights into circuit abnormalities in autism.

18 April 2023

Pyramidal neurons in normal mice and mice with autism-like symptoms.
Layer 5 pyramidal neurons in normal mice (left) compared with mice with autism gene knocked-out (right), showing a patch of disorganized cortex. (Microscopic image: IOB)

A research team led by Professor Botond Roska at the Institute of Molecular and Clinical Ophthalmology Basel (IOB) and the University of Basel has studied circuits in the brains of living mouse embyros. They discovered a previously unknown, early active circuit in the cerebral cortex. Genetic disruption of this circuit leads to changes similar to those seen in brains of people with autism. The team reports these findings in the scientific journal "Cell".

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 reeesearch team studied when and how these neurons assemble into the first active circuits in the cortex.

“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 professor at the Faculty of Medicine, University of Basel. 

Active earlier than expected

The prevailing view is that the cortex develops in an “inside out fashion”, with the deepest of its six layers appearing first. Therefore, 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 Dr. Arjun Bharioke, a systems neuroscientist and one of the paper’s two lead authors. The team discovered a very early transient circuit that was already highly active and correlated even before the six-layer cortex had formed.

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