American researchers have kept a tiny cochlea sliver from a gerbil alive and functional outside of the body for the first time and watched it work in real time as they played sounds from a speaker to it.
The Rockefeller University scientists designed a chamber which imitated the living environment of the cochlea and placed a sliver of cochlea tissue inside.
They played sounds via a tiny speaker to the cochlea. The researchers said they witnessed the opening and closing of ion channels in hair bundles (protruding from hair cells) add energy to sound-driven vibrations, amplifying them. They also saw how outer hair cells elongated and contracted in response to voltage changes through electromotility.
“We could see in fine detail what every piece of the tissue was doing at the subcellular level,” said postdoctoral fellow Dr Francesco Gianoli on The Rockefeller University news website.
“We can now observe the first steps of the hearing process in a controlled way that was previously impossible.”
The chamber reproduces the living environment of the sensory tissue, including continuously bathing it in nutrient-rich liquids called endolymph and perilymph and maintaining its native temperature and voltage.
The device allowed the scientists to capture live biomechanics of the rodent cochlea’s auditory powers, including exceptional sensitivity, sharp frequency tuning, and the ability to encode a broad range of sound intensities.
Dr Gianoli is co-author of two studies in PNAS and Hearing Research which described the “remarkable advancement” achieved by neuroscientist Dr A. James ‘Jim’ Hudspeth and his team at the university’s Laboratory of Sensory Neuroscience.
Dr Hudspeth had been working on this for more than 20 years, said Rockefeller biophysicist Professor Marcelo Magnasco who described it as “a crowning achievement for a remarkable career”. Dr Hudspeth and his team achieved the breakthrough shortly before his death in August 2025.
The university said the innovation was a product of Dr Hudspeth’s five decades of work illuminating molecular and neural mechanisms of hearing – insights that had illuminated new paths to preventing or reversing hearing loss.
The researchers said the breakthrough also provided direct evidence of a unifying biophysical principle that governed hearing across the animal kingdom. They hope it may improve understanding of cellular mechanisms behind hearing and its loss.
Mechanics of hearing
They said the cochlea’s fragility and inaccessibility embedded in the densest bone in the body made it difficult to study in action.
Most hearing loss resulted from damage to hair cells that lined the cochlea, they added. The cochlea has 16,000 hair cells and each bundle is a tuned machine that amplifies and converts sound vibrations into electrical responses that the brain can interpret.
It was well documented that in insects and non-vertebrate animals such as the bullfrogs studied in Hudspeth’s lab, a biophysical phenomenon known as a Hopf bifurcation was key to the hearing process, they said in the media release.
The Hopf bifurcation described a mechanical instability or tipping point between complete stillness and oscillations. “At this knife-edge, even the faintest sound tips the system into movement, allowing it to amplify weak signals far beyond what would otherwise register,” they said.
In the bullfrog cochlea, the instability was in bundles of sensory hair cells, which were primed to detect incoming sound waves. When waves hit, the hair cells moved, amplifying the sound through an active process, the researchers added.
Biophysicist Professor Marcelo Magnasco, head of the Rockefeller’s Laboratory of Integrative Neuroscience, collaborated with Dr Hudspeth on some of his seminal findings.
“This study is a masterpiece and in the field of biophysics, it’s one of the most impressive experiments of the last five years,” Prof Magnasco said.
The pair documented the existence of the Hopf bifurcation in the bullfrog cochlea in 1998 but to determine if it existed in the mammalian cochlea, the team needed to observe the active process in a mammalian cochlea in real time and at a greater level of detail than before.
Similar across mammals
They used cochlea of gerbils, whose hearing falls in a similar range as humans, and excised slivers no larger than 0.5 mm in the region that picks up the middle range of frequencies. They timed their excision to a developmental moment in which the gerbil’s hearing was mature, but the cochlea had not fully fused to the temporal bone.
Mr Brian Fabella, research specialist in the Hudspeth lab, and instrumentation engineer Mr Nicholas Belenko, from Rockefeller’s Gruss Lipper Precision Instrumentation Technologies Resource Center, helped develop the chamber.
The researchers found that key to the active process was a Hopf bifurcation tipping point that turned mechanical instability into sound amplification.
“This shows that the mechanics of hearing in mammals is remarkably similar to what has been seen across the biosphere,” said co-first author Mr Rodrigo Alonso, a research associate in the lab.
The scientists anticipate experimentation using the ex vivo cochlea will improve their understanding of hearing and hopefully point to better therapies.
“For example, we will now be able to pharmacologically perturb the system in a very targeted way that has never been possible before, such as by focusing on specific cells or cell interactions,” Alonso said.
