Sat, 28 Jan 2023

Washington [US], January 22 (ANI): Specialized synapses in our sensory organs enable us to walk, dance, and tilt our heads without experiencing vertigo or losing our balance. These synapses process messages more quickly than any other part of the human body.

A small team of neuroscientists, physicists, and engineers from various institutions made a discovery that took more than 15 years to develop. By unlocking the synapses' mechanism, they opened the door for future research that could lead to better treatments for vertigo and balance disorders, which affect up to one in three Americans over the age of 40.

The new study in the Proceedings of the National Academy of Sciences describes the workings of "vestibular hair cell-calyx synapses," which are found in organs of the innermost ear that sense head position and movements in different directions.

"Nobody fully understood how this synapse can be so fast, but we have shed light on the mystery," said Rob Raphael, a Rice University bioengineer who co-authored the study with the University of Chicago's Ruth Anne Eatock, the University of Illinois Chicago's Anna Lysakowski, current Rice graduate student Aravind Chenrayan Govindaraju and former Rice graduate student Imran Quraishi, now an assistant professor at Yale University.

Synapses are biological junctions where neurons can relay information to one another and other parts of the body. The human body contains hundreds of trillions of synapses, and almost all of them share information via quantal transmission, a form of chemical signaling via neurotransmitters that requires at least 0.5 milliseconds to send information across a synapse.

Prior experiments had shown a faster, "nonquantal" form of transmission occurs in vestibular hair cell-calyx synapses, the points where motion-sensing vestibular hair cells meet afferent neurons that connect directly to the brain. The new research explains how these synapses operate so quickly.In each, a signal-receiving neuron surrounds the end of its partner hair cell with a large cuplike structure called a calyx. The calyx and hair cell remain separated by a tiny gap, or cleft, measuring just a few billionths of a meter.

"The vestibular calyx is a wonder of nature," Lysakowski said. "Its large cup-shaped structure is the only one of its kind in the entire nervous system. Structure and function are intimately related, and nature obviously devoted a great deal of energy to produce this structure. We've been trying to figure out its special purpose for a long time."From the ion channels expressed in hair cells and their associated calyces, the authors created the first computational model capable of quantitatively describing the nonquantal transmission of signals across this nanoscale gap. Simulating nonquantal transmission allowed the team to investigate what happens throughout the synaptic cleft, which is more extensive in vestibular synapses than other synapses.

"The mechanism turns out to be quite subtle, with dynamic interactions giving rise to fast and slow forms of nonquantal transmission," Raphael said. "To understand all this, we made a biophysical model of the synapse based on its detailed anatomy and physiology."The model simulates the voltage response of the calyx to mechanical and electrical stimuli, tracking the flow of potassium ions through low-voltage-activated ion channels from pre-synaptic hair cells to the post-synaptic calyx.

Raphael said the model accurately predicted changes in potassium in the synaptic cleft, providing key new insights about changes in electrical potential that are responsible for the fast component of nonquantal transmission; explained how nonquantal transmission alone could trigger action potentials in the post-synaptic neuron; and showed how both fast and slow transmission depend on the close and extensive cup formed by the calyx on the hair cell.Eatock said, "The key capability was the ability to predict the potassium level and electrical potential at every location within the cleft. This allowed the team to illustrate that the size and speed of nonquantal transmission depend on the novel structure of the calyx. The study demonstrates the power of engineering approaches to elucidate fundamental biological mechanisms, one of the important but sometimes overlooked goals of bioengineering research."Quraishi began constructing the model and collaborating with Eatock in the mid-2000s when he was a graduate student in Raphael's research group and she was on the faculty of Baylor College of Medicine, just a few blocks from Rice in Houston's Texas Medical Center.

Raphael said the model opens the door for a deeper exploration of information processing in vestibular synapses, including research into the unique interactions between quantal and nonquantal transmission.He said the model could also be a powerful tool for researchers who study electrical transmission in other parts of the nervous system, and he hopes it will aid those who design vestibular implants, neuroprosthetic devices that can restore function to those who have lost their balance. (ANI)

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