In a new study, researchers from King's College London have found that brain connectivity (brain wiring) needs to control local protein synthesis at the level of specific synaptic types. They indicate that the regulation of protein synthesis occurs in a highly specific manner, with the extent related to the type of synapse involved. They identified a signaling pathway that controls synapse formation between excitatory pyramidal cells and inhibitory interneurons expressing parvalbumin (parvalbumin). This is the first study confirming the existence of this specificity in the regulation of protein synthesis during brain wiring. The relevant study results were published in the Science journal, dated November 25,2022, with the paper title "Cortical wiring by synapse type specific control of local protein synthesis".
The cerebral cortex is the outer layer of the largest part of the human brain, the telencephalon (cerebrum). It is responsible for our most complex and diverse behaviors through the control of motor and sensory functions. It is also one of the most complex biological systems, so understanding the developmental mechanisms that control it is a major scientific challenge.
There are two major types of neurons in the cerebral cortex: excitatory pyramidal cells and inhibitory interneurons. Their interaction is essential for the proper functioning of the cerebral cortex. Inhibitory interneurons regulate and synchronize the activity of excitatory pyramidal cells to coordinate their behavior.
Neurons in the cerebral cortex assemble into neural networks through connections called synapses. Like electrical connections, synapses consists of presynaptic chambers (power plug) and retrosynaptic compartments (socket). In the adult brain, protein synthesis occurs locally in both regional compartments to perform neuronal function.
Controlling the synthesis of specific proteins through chemical signaling enables the brain to regulate the activity of individual synapses. However, how this modulation varies between the two types of developing cortical neurons is not fully understood.
Dr. Clemence Bernard, lead author of the Institute of Psychiatry, Psychology and Neuroscience at King's College London, London, said, " Exploring the molecular processes regulating the generation of cortical connectivity is exciting, especially when they end up so specific. We identified a signaling pathway that controls synaptic-in-protein synthesis formed by one of the most fundamental connections in the cerebral cortex, excitatory pyramidal cells, and inhibitory interneurons expressing paralbumin.”
Abnormal protein synthesis at synapses is a central mechanism of autism spectrum disorder (ASD). The mechanisms identified in this new study reveal interactions between proteins associated with neurodevelopmental disorders. This finding supports the idea that synapses formed by excitatory pyramidal cells and paralbumin-expressing inhibitory interneurons may be particularly sensitive to the dysregulation seen in brain developmental disorders, such as ASD.
Professor Oscar Marin, co-corresponding author of the Institute of Psychiatry, Psychology and Neuroscience at King's College London, London, said, " It is fascinating that many of the genes involved in ASD seem to be regulated by the same signaling pathway that we found in this study.”
Professor Beatriz Rico, co-corresponding author of the paper and the Institute of Psychiatry, Psychology and Neuroscience at King's College London, said, " This observation suggests that the connection between excitatory pyramidal cells and inhibitory paralbumin-expressing interneurons may be a hotspot for multiple genetic risk factors in ASD."
