Transcriptional control of sound discrimination

February 3, 2017, Friedrich Miescher Institute for Biomedical Research
Transcriptional control of sound discrimination
How does that sound? Hox2 transcription factors control sound discrimination in the cochlear nucleus. Credit: Friedrich Miescher Institute for Biomedical Research

Filippo Rijli and his team at the Friedrich Miescher Institute for Biomedical Research have identified two genes that control sound discrimination in the brain. The Hox2 transcription factors act in the mouse brain stem and ensure that the auditory neurons are precisely connected from the inner ear to higher brain areas. In their absence, mice were still able to hear but no longer able to discern sounds with close, yet distinct, frequencies.

While we listen to Beethoven, a second highly sophisticated orchestra of interconnected neurons between the ear and the ensures that we can indeed discern the different sounds and cherish the nuances of the play.

This network of neurons connects the snail like structure called cochlea of the inner ear with higher brain regions. These neurons are spatially arranged in a topographic map such that sounds with close, though distinct, frequencies are processed in neighboring neuronal cascades. This organizing principle called tonotopy is preserved in all associated higher brain areas from brainstem to midbrain to cortex. Little is known about the molecular control of such a sophisticated arrangement of axons and synapses.

Filippo Rijli and his team at the Friedrich Miescher Institute for Biomedical Research (FMI) have now identified two paralogue transcription factors (Hoxa2 and Hoxb2, collectively called Hox2) with an important role in setting up these precise tonotopic connections in the brainstem cochlear nuclei.

In the cochlear nucleus, each axon coming from the inner ear relaying information about a specific sound frequency mainly interacts with one neuron through one giant synapse, the endbulb of Held synapse. This ensures that the sound information from the outside world is relied properly and precisely in the brain. Neurons that receive the same sound information (i.e. that respond to the same frequency) are next to each other, they form bands in the cochlear nucleus.

In the absence of Hox2 transcription factors, this one-to-one connection is disturbed, the bands become fuzzy. Kajari Karmakar, former FMI PhD student and first author of the study explains: "Suddenly, in the cochlear nucleus receive input from multiple smaller synapses." This perturbs sound precision: "We could show in collaboration with the laboratory of Andreas Luthi that mice that lack Hox2 in the can no longer discriminate sounds with close, yet distinct, frequencies," continues Karmakar.

"These results show nicely the importance of post-synaptic transcriptional regulation for the precision of connectivity in this sensory circuit and for the processing of sound information in the brain", explains Rijli, "In addition, these findings might also advance our understanding of the genetic basis of central auditory processing disorders (CAPD) in children." In these children, peripheral hearing is intact but the processing of the auditory information is impaired.

Explore further: All in the timing: Mapping auditory brain cells for maximum hearing precision

More information: Kajari Karmakar et al. Hox2 Genes Are Required for Tonotopic Map Precision and Sound Discrimination in the Mouse Auditory Brainstem, Cell Reports (2017). DOI: 10.1016/j.celrep.2016.12.021

Related Stories

All in the timing: Mapping auditory brain cells for maximum hearing precision

September 12, 2016
When it comes to hearing, precision is important. Because vertebrates, such as birds and humans, have two ears—and sounds from either side travel different distances to arrive at each one - localizing sound involves discerning ...

Rewired visual input to sound-processing part of the brain leads to compromised hearing

August 22, 2012
Scientists at Georgia State University have found that the ability to hear is lessened when, as a result of injury, a region of the brain responsible for processing sounds receives both visual and auditory inputs.

Ear delivers sound information to brain in surprisingly organized fashion: study

June 5, 2012
The brain receives information from the ear in a surprisingly orderly fashion, according to a University at Buffalo study scheduled to appear June 6 in the Journal of Neuroscience.

Cochlear implants for advanced hearing loss

November 11, 2016
Dear Mayo Clinic: I'm 72 and have worn hearing aids for about a decade. Over the past several years, my hearing seems to be getting worse. Although I've tried several different kinds of hearing aids, I can't hear well with ...

Mapping face sensation in the brainstem

October 23, 2015
Filippo Rijli and his group at the FMI have shown how the formation of a sensory topographic map in the brainstem is controlled by a single transcription factor, thus shedding light on a decades-old question in neuroscience. ...

Recommended for you

Rare in-vivo study shows weak brain nodes have strong influence on memory network

June 20, 2018
Our ability to learn, remember, problem solve, and speak are all cognitive functions related to different parts of our brain. If researchers can identify how those brain parts communicate and exchange information with each ...

A dual-therapy approach to boost motor recovery after a stroke

June 20, 2018
Paralysis of an arm and/or leg is one of the most common effects of a stroke. But thanks to research carried out by scientists at the Defitech Foundation Chair in Brain-Machine Interface and collaborators, stroke victims ...

Powerful new approach helps understand molecular alterations in neurological disease

June 20, 2018
Neurological diseases are typically associated with a multitude of molecular changes. But out of these thousands of changes in gene expression, which ones are actually driving the disease? To answer this question, a team ...

Scientists unravel DNA code behind rare neurologic disease

June 20, 2018
Scientists conducting one of the largest full DNA analyses of a rare disease have identified a gene mutation associated with a perplexing brain condition that blinds and paralyzes patients.

New technique fine-tunes treatment for severe epilepsy cases

June 20, 2018
One of three epilepsy patients experience no relief from drugs and are candidates for surgery. An advance by researchers at Yale and the Cleveland Clinic will enable surgeons to more precisely target areas of the brain causing ...

Absence epilepsy—when the brain is like 'an orchestra without a conductor'

June 20, 2018
At first, the teacher described her six-year-old student as absentminded, a daydreamer. The boy was having difficulty paying attention in class. As the teacher watched the boy closely, she realized that he was not daydreaming. ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.