Essential Signaling Pathway for Neuronal Connectivity During Brain Development Identified

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

Source: King’s College London

Recent research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London has shown that the electrical brain has the ability to control local protein synthesis at the level of specific synapse types.

In new research published in Sciencea joint study between the Rico and Marín groups showed that protein synthesis is regulated in a very specific way, at the level of the type of synapse involved.

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

This is the first study to show how such a species is involved in regulating protein synthesis during the brain cycle.

The cerebral cortex is the outer layer of the main part of the human brain, the cerebrum. It is responsible for our extreme and varied behaviors through its control of motor and emotional functions. It is one of the most complex biological systems, so understanding the mechanisms that drive its development is a major scientific challenge.

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There are two main types of neurons in the cerebral cortex: excitatory pyramidal cells and inhibitory interneurons. The interaction between each part is important for the normal functioning of the cerebral cortex. Inhibitory interneurons speed up and regulate the activity of excitatory neurons, thereby regulating their behavior.

Neurons in the cerebral cortex are organized into cells held together by connections called synapses. Like electrical connections, synapses have pre- (power plug) and post-synaptic (socket) compartments. In the adult brain, protein synthesis occurs in two areas to support the function of neurons.

Controlling the synthesis of specific proteins, through chemical signaling, allows the brain to regulate the functions of individual synapses. How this regulation differs between the two types of developing cerebral cortex neurons, however, is not fully understood.

This represents the synapses
A confocal microscopy image showing isolated cortical synapses with presynapses in magenta and postsynapses in cyan. Location: King’s College London

“Finding the molecular processes that regulate the development of cortical connections is exciting, especially when they end up in a specific area. We discovered a signaling pathway that controls the protein synthesis in one of the main connections in the cerebral cortex, the synapses formed by the pyramidal cells on the parvalbumin interneurons,” said Dr. Clémence Bernard, first author of the study from King’s IoPPN.

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Abnormal protein synthesis in synapses is a critical mechanism underlying ASD. The mechanism identified in this paper shows an interaction of proteins related to neurodevelopmental diseases. This finding supports the idea that synapses formed by excitatory pyramidal neurons and parvalbumin-positive interneurons may be susceptible to the dysregulation seen in developmental brain conditions such as ASD.

“It’s good that many of the genes involved in ASD seem to be regulated by the same signaling pathway that we found in this study,” said Professor Marín, one of the two senior authors of the study.

“This finding shows the interactions between excitatory pyramidal neurons and inhibitory interneurons, suggesting that parvalbumin is a hot spot for the many genetic risk factors in ASD,” said Professor Rico. the main author of the study.

About this neuroscience research news

Author: Printing Office
Source: King’s College London
Contact: Press Office – King’s College London
Image: Image courtesy of King’s College London

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Basic research: Entry is restricted.
“Cortical wiring as a synapse-specific control of local protein synthesis” by Clémence Bernard et al. Science

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Cortical wiring as a synapse-specific control of local protein synthesis

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

We identify a signaling pathway that regulates the local synthesis of proteins required to form excitatory synapses in parvalbumin-expressing (PV).+) interneurons in the rat cerebral cortex.

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

Ribosome-based mRNA profiling reveals a molecular program of synaptic proteins downstream of ErbB4 signaling that is required to produce excitatory inputs in PV.+ interneurons.

Therefore, specific interactions use local protein synthesis to inhibit synapse formation in the nervous system.


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