Brain Conductors Find Precise Connection to Target Cells via Protein Handshake

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Brain Conductors Find Precise Connection to Target Cells via Protein Handshake

Summary: Researchers have identified two specific proteins, gliomedin and CNTNAP4, that act as a “handshake” mechanism allowing inhibitory chandelier cells to connect precisely with excitatory pyramidal neurons. This connection is vital for maintaining electrical balance in the brain. Disruptions in this process are linked to neurological disorders such as epilepsy, schizophrenia, and autism.

Source: Ohio State University

The brain’s ability to process information relies on a delicate balance between neurons that send “go” signals and those that send “stop” signals. Now, researchers have discovered exactly how the “conductors” of this orchestra find their way to the podium.

A new study from Ohio State University reveals how chandelier cells—a class of inhibitory interneurons—link up with their target excitatory cells. The team identified two specific molecules that must be present to enable a “handshake” between the cells, allowing synapses to form.

Chandelier cells are critical for brain function. They connect to a specific location on target excitatory neurons (pyramidal cells) called the axon initial segment. By grabbing this “handle,” chandelier cells can powerfully suppress the activity of the excitatory neurons, effectively preventing runaway electrical signals.

“These inhibitory interneurons shape and balance local circuit activity – they are the modulators, coordinators, the conductors of the orchestra,” said Yasufumi Hayano, lead author and postdoctoral scholar at Ohio State University. “From our results, we’ve concluded that interaction between two specific proteins regulates the specificity of their synapse formation.”

Loss of coordination between these cell types is associated with severe neurological and psychiatric disorders, including epilepsy, depression, autism, and schizophrenia.

The Molecular Handshake

The researchers discovered that the connection relies on a precise molecular interaction. The study identified two key proteins:

• CNTNAP4: Located on the chandelier cells (the “conductors”).
• Gliomedin: Located on the axon initial segment of the target neurons.

When these two proteins meet, they facilitate the formation of the synapse. Using visualizations in the brains of young mice, the team observed that when the genes for gliomedin were removed, the chandelier cells failed to form adequate connections with their targets. The “handshake” was broken, leaving the “conductors” unable to control the orchestra.

Implications for Neurological Disorders

Because the axon initial segment is the exact site where neurons generate action potentials (the signals used to communicate), chandelier cells have a disproportionately strong influence on brain activity. They essentially control the “faucet” of information flow.

“This is basic neuroscience, but there might be an impact for neuronal disorders,” said Hayano. “If this process is disrupted, what happens? If we lose those genes, which neuronal disorder might occur? We still don’t know, but those possibilities should be explored.”

Senior author Hiroki Taniguchi noted that understanding these developmental mechanisms is the first step toward identifying therapeutic targets for conditions where brain circuitry is imbalanced.

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About this neuroscience research news

Author: Media Relations
Source: Ohio State University
Contact: Emily Caldwell – Ohio State University
Image: The image is credited to Ohio State University

Original Research: Closed access.
“The highly localized interaction between Neurofascin-186 and Gliomedin promotes subcellular innervation by the chandelier cell” by Yasufumi Hayano et al. The Journal of Neuroscience