The organ that allows us to walk, dance, and turn our heads without dizziness, the inner ear needs speed or imbalance has unique synapses that process signals faster than anything else in the human body.
In research that took more than 15 years, a small group of scientists, scientists and engineers from different industries opened the system of synapses, opening the way for research that could improve treatment for vertigo and dizziness, balance that affects up to 1 out of 3 in America over 40 years.
A new study published in the Proceedings of the National Academy of Sciences describes the role of ‘vestibular hair cell-calyx synapses’, which are located in the inner ear part that perceives the main position and movement.
“No one fully understands how fast this synapse can be, but we have increased the mystery,” said Rob Raphael, a Rice University bioengineer who co-authored the study with Ruth Anne Eatock, from the University of Chicago. , University of Illinois at Chicago. 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 living connections where neurons can transmit information to each other and to other parts of the body. The human body has hundreds of trillions of synapses, and almost all of them share information through quantum transmission, a type of chemical signaling through neurotransmitters that takes at least 0.5 milliseconds to send information across a synapse.
Previous experiments have shown that a fast, “non-quantum” type of transmission occurs at vestibular hair cell-calyx synapses, the point where excitable vestibular hair cells meet afferent neurons that connect directly to the brain. The new research explains how quickly these synapses work.
In each, the neuron receives the signal around the end of the hair cell and a large cup-shaped structure called the calyx. The calyx is separated from the hair cell by a small gap, or division, which is only a few billionths of a meter.
“The vestibular calyx is a natural wonder,” Lysakowski said. “Its large cup-like structure is unique in the entire nervous system. Design and function are closely related, and nature has invested a lot of energy in creating this structure. We have been trying for a long time to understand its exact purpose.
With ion channels shown in hair cells and their associated calyxes, the authors created the first computational model able to quantify the non-quantum transmission of signals through this space at the nanoscale. The transition to non-quantum transmission allowed the team to study what happens in synaptic bursts, which are greater in vestibular synapses than in other synapses.
“The process becomes more subtle, with stronger relationships resulting in slower and faster forms of communication,” Raphael said. “To understand all this, we developed a biophysical model of the synapse based on a detailed description of anatomy and physiology.”
The model simulates the voltage response of the calyx to electrical stimuli, by following potassium ions through low voltage-activated ion channels from pre-synaptic to post-synaptic hair cells Calyx.
Raphael said that the model accurately predicted potassium changes in synaptic bursts, providing important new insights into the electrical changes that can cause rapid non-quantum transmission; explained how non-quantum communication can trigger action potentials in post-synaptic neurons; and show how fast and rapid the transmission depends on the narrow and wide cup formed by the calyx and the hair cell.
Eatock said: “The main ability is the ability to predict the level of potassium and electrical potential at any point in space. This allowed the team to demonstrate that the size and speed of non-quantum transmission depends on the new structure of the calyx. The study demonstrated the power of engineering methods to define basic biological processes, one of the important but sometimes overlooked goals of bioengineering research.
Quraishi began building a model and collaborating with Eatock in the mid-2000s when he was a graduate student in Raphael’s research group and was on the faculty at Baylor College of Medicine, far away. Rice House at Texas Medical Center in Houston.
His first version of the model captured an important part of the synapse, but he said that differences in “our knowledge of specific potassium channels and other factors make the model too limited to be accurate.” good.”
Since then, Eatock, Lysakowski and others have discovered ion channels in the calyx that changed scientists’ understanding of how water passes through the hair cells and the calyx membrane.
“I was surprised by the unfinished work,” said Qurashi, who was relieved and happy when Govindaraju, a Ph.D. studying physics, joined Raphael’s lab and resumed work on models. in 2018.
“When I started this project, a lot of data supported non-quantum propagation,” Govindaraju said. “But the process, especially of fast transmission, is not clear. Creating the model allowed us to better understand the relationship and purpose of different ion channels, the structure of the calyx, and the dynamic changes in potassium and electrical power in the synaptic cleft.
Raphael said: “One of my first contributions was the creation of an ion transport model in the inner ear. It is always satisfying to arrive at a unified mathematical model of such a complex system. For the past 30 years, since the first discovery of non-quantum communication, scientists have wondered, “Why is this synapse so fast?” and “does baud rate affect the special structure of the calyx?”. We have provided answers to these two questions. ”
He said that the relationship between the structure and function of the calyx “is an example of how evolution promotes morphological specialization. A strong argument can be made that once animals emerge from the sea and start moving on land, swinging on trees and flying, the vestibular system is called upon to quickly inform the brain of head position. in the sky. But the chalice appeared.
Raphael said the model paves the way for further investigation of information processing at vestibular synapses, including research into the unique relationship between quantum and non-quantum communication. ”
When I started this project, a lot of data supported non-quantum propagation,” Govindaraju said. “But the process, especially of rapid delivery, is not clear. The construction of the model allowed us to better understand the relationship and purpose of the various ion channels, the structure of the calyx and the changes in potassium and electricity in the synaptic cleft.
Raphael said: “One of my first contributions was the creation of an ion transport model in the inner ear. It is always satisfying to arrive at a unified mathematical model of such a complex system. For the past 30 years – since the first discovery of non-quantum communication – scientists have wondered, “Why is this synapse so fast?” and “does the baud rate affect the chalice’s unique structure?” We have provided answers to these two questions. ”
He said that the connection between the calyx system and function “is an example of how evolution leads to morphological specialization. A strong argument can be made that once animals came out of the sea and began to move on land, and -flying in trees and flying, the vestibular system is increasingly called to tell the brain quickly about the position of the head in space. But the chalice appeared.
Raphael said the model paves the way for further investigation of information processing at vestibular synapses, including research into the unique relationship between quantum and non-quantum communication.
