Embryonic Mouse Brains Reveal Information about Neurodevelopmental Circuitry

Researchers at the Institute of Molecular and Clinical Ophthalmology Basel have identified an active multi-layer circuit that forms in the cortex during an early stage of development using a new approach to analyzing live embryonic mouse brains at single-cell resolution. The findings, published in Cell, confirm that understanding the cortical development of various cell types and circuits can provide insight into neurodevelopmental diseases. 

Autism is associated with faulty cortex circuitry, which governs sensory perception, cognition, and other high-order functions. The team focused on studying when and how pyramidal neurons assemble into the first active circuits in the cortex.

They discovered that there was already a highly active, transient circuit composed of embryonic near-projecting-type neurons, even before the six-layer cortex had formed, indicating that the neurons were already connected before their migration to form layer 5. The transient circuit initially had two layers: a deep layer and a superficial layer, with the superficial layer becoming silent and vanishing later.

The team then worked with knockout mouse lines missing one or both alleles of two autism-associated genes, Chd8 and Grin2b, and discovered that in homozygous and heterozygous knockout mice, the superficial layer remained active as a developmental remnant throughout embryonic development, never disappearing.

The knockout mouse brains contained patchy areas of cortical disorganization like those observed in people with autism. These findings suggest that this newly found circuit regulates the spatial organization of pyramidal neurons and that changes to embryonic circuits might play a role in dysfunctions associated with neurodevelopmental disorders.

The researchers will continue to study this circuitry’s superficial and deep layers to learn more about the etiology of neurodevelopmental diseases. This study provides essential insights into the development of cortical circuits and how they relate to neurodevelopmental disorders, such as autism. Further understanding of these circuits could potentially lead to better treatments and therapies for those affected.