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Signaling pathway essential for neural connectivity identified during brain development – Neuroscience News

Summary: The study reveals a signaling pathway that controls the formation of synapses between pyramidal neurons and inhibitory neurons expressing the protein parvalbumin.

Source: King’s College London

New research from the Institute of Psychiatry, Psychology and Neuroscience (IoPPN) at King’s College London has demonstrated that brain wiring requires the control of local protein synthesis at specific types of synapses.

In new research published in Sciencea collaborative study between the Rico and Marín groups reported that the regulation of protein synthesis occurs in very specific ways, depending on the type of synapse involved.

The authors identified a signaling pathway controlling the formation of synapses between excitatory pyramidal cells and inhibitory interneurons expressing the protein parvalbumin.

This is the first study that demonstrates the presence of such specificity in the regulation of protein synthesis during brain wiring.

The cerebral cortex is the outer layer of the largest part of the human brain, the cerebrum. It is responsible for our most sophisticated and diverse behaviors through its control of motor and sensory functions. It is also one of the most complex biological systems, understanding the mechanisms that control its development is therefore a major scientific challenge.

There are two main types of neurons in the cerebral cortex: excitatory pyramidal cells and inhibitory interneurons. The interaction between each part is crucial for the normal functioning of the cerebral cortex. Inhibitory interneurons pace and synchronize the activity of excitatory neurons, thus orchestrating their behavior.

The neurons of the cerebral cortex are organized in networks wired by connections called synapses. Like an electrical connection, synapses consist of pre- (power socket) and post-synaptic (socket) compartments. In the adult brain, protein synthesis occurs locally in both compartments to ensure neuron function.

Controlling the synthesis of specific proteins, through chemical signaling, allows the brain to regulate the activities of individual synapses. However, how this regulation differs between two types of neurons in the developing cerebral cortex has not been fully understood.

This shows the synapses
A confocal microscopy image illustrating isolated cortical synapses with presynapses in magenta and postsynapses in cyan. Credit: King’s College London

“Exploring the molecular processes regulating the development of cortical connectivity is exciting, especially when they end up being so specific. We have identified a signaling pathway that controls protein synthesis in one of the most fundamental connections in the cerebral cortex, the synapses formed by pyramidal cells on parvalbumin interneurons,” explains Dr Clémence Bernard, first author of the King’s IoPPN study.

Abnormal protein synthesis in synapses is a central mechanism underlying ASD. The mechanism identified in this article reveals an interaction of proteins associated with neurodevelopmental disorders. This finding supports the idea that synapses made by excitatory pyramidal cells and parvalbumin-positive interneurons may be particularly sensitive to the dysregulation observed in developmental brain conditions such as ASD.

“It is fascinating that many ASD-related genes appear to be regulated by the same signaling pathway that we identified in this study,” says Professor Marín, one of the study’s two lead authors.

“This observation suggests that connections between excitatory pyramidal cells and parvalbumin-expressing inhibitory interneurons are a possible hotspot for multiple genetic risk factors in ASD,” says Professor Rico, co-lead author of the study.

About this neuroscience research news

Author: Press office
Source: King’s College London
Contact: Press Office – King’s College London
Image: Image is credited to King’s College London

Original research: Access closed.
“Cortical wiring by synapse type-specific control of local protein synthesis” by Clémence Bernard et al. Science

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Cortical wiring by synapse type-specific control of local protein synthesis

Neurons use local protein synthesis to support their morphological complexity, which requires independent control over multiple subcellular compartments down to the level of individual synapses.

We identify a signaling pathway that regulates the local synthesis of proteins necessary for the formation of excitatory synapses expressing parvalbumin (PV+) interneurons in the cerebral cortex of mice.

This process involves the regulation of the TSC 2 (Tsc2) subunit by the Erb-B2 receptor tyrosine kinase 4 (ErbB4), which allows local control of messenger RNA {mRNA} translation in a system-specific manner. cell type and synapse type.

Profiling of ribosome-associated mRNA reveals molecular program of synaptic proteins downstream of ErbB4 signaling required to form excitatory inputs on PV+ interneurons.

Thus, specific connections use local protein synthesis to control the formation of synapses in the nervous system.

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