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Unpacking How We Hear: The Role of Neurons

A closer look at how neurons influence our hearing ability.

― 6 min read


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Table of Contents

The ability to hear is a complex process that involves many different parts of the ear and brain. One important part of this system involves tiny structures in the inner ear called Outer Hair Cells (OHC). These cells help amplify sounds so that we can hear better. This amplification is controlled by signals from the brain that can either enhance or reduce the activity of OHCs, allowing us to focus on important sounds while reducing background noise.

The Role of Cochlear Amplification

Cochlear amplification refers to the processes that enhance sound signals in the inner ear. The outer hair cells play a key role in this process. They respond to sound inputs and change their shape, which can help boost the vibrations that travel through the ear. This makes softer sounds easier to hear. In addition to enhancing sound, there are also mechanisms in place to help protect our hearing from loud noises.

Feedback from Medial Olivocochlear Neurons

The brain sends feedback to outer hair cells through a group of neurons known as medial olivocochlear (MOC) neurons. These neurons can inhibit the activity of outer hair cells. When this happens, the vibrations in the cochlea are reduced, which helps to filter out background noise. This feedback is crucial for allowing us to focus on specific sounds, especially in noisy environments.

Listening in Noise

Listening in noisy places can be challenging. MOC neurons play a role in helping us hear important sounds better by suppressing unwanted noise. However, the details of how the signals from MOC neurons influence the outer hair cells are not entirely understood. Researchers have identified that certain cells in the cochlear nucleus send signals to the MOC neurons, but the full picture of how all these connections work together is still being explored.

Experimenting with Brain Slices

To understand how MOC neurons work, researchers use brain slice preparations from mice. These slices are thin sections of brain tissue that allow scientists to study the connections and functions of neurons in a controlled environment. By using advanced techniques, they can stimulate specific pathways and record how the neurons respond.

The Wedge-Slice Preparation

A new type of brain slice called a "wedge-slice" helps maintain the circuitry that carries sound information to the MOC neurons. This preparation allows researchers to study how Excitatory (stimulating) and Inhibitory (suppressing) signals interact to affect the activity of MOC neurons.

Stimulating the Midline

In experiments, researchers stimulated neurons at the midline of the wedge-slice to bypass certain circuits. By examining the responses of MOC neurons to this stimulation, they discovered that the signals traveling through different pathways can have distinct effects. They found that the pathways providing inhibitory signals to MOC neurons are very fast and can help control the timing of sound processing.

Excitatory and Inhibitory Inputs

Stimulation near the midline caused MOC neurons to receive both excitatory and inhibitory signals. The researchers observed that excitatory signals arrived more quickly than inhibitory ones. This difference is significant, as it plays a role in how quickly the MOC neurons can respond to sounds.

Specific Pathways

Different pathways in the auditory system have unique characteristics. The pathway that includes the medial nucleus of the trapezoid body (MNTB) and the MOC neurons is particularly fast and precise. This precision is important for allowing the auditory system to process sounds quickly and accurately.

Calibrating Sound Responses

Researchers also wanted to ensure that the electrical stimulation in their experiments was indeed activating the appropriate neurons through synaptic connections, rather than causing direct activation that could bypass normal processing. By using calcium imaging techniques, they could observe how certain neurons reacted to stimulation, further confirming the connections between various parts of the auditory system.

Assessing Synaptic Inputs

In studies where they stimulated the auditory nerve, researchers recorded the activity of MOC neurons. They found that the timing of excitatory and inhibitory signals was affected by how stimulation was applied. When using the auditory nerve stimulation, they created a more realistic representation of how these neurons would respond in a living animal compared to midline stimulation.

Patterns of Activity in MOC Neurons

As they explored the synaptic responses, researchers noted that MOC neurons showed different patterns of activity based on stimulation methods. Some neurons showed mixed responses, indicating complex interplay between excitatory and inhibitory inputs. These variations are likely influenced by the specific pathways being activated.

The Importance of E-I Balance

The balance between excitatory and inhibitory signals is crucial for the proper functioning of MOC neurons. The timing of these signals can influence how MOC neurons respond to sounds and how they modulate the activity of outer hair cells in the cochlea.

Investigating E-I Timing

In their computational models, researchers simulated how changes in the timing of excitatory and inhibitory signals might affect MOC neuron activity. By manipulating the timing of these signals, they were able to observe how MOC neurons responded in various scenarios. This modeling work helps to better understand the dynamic nature of synaptic input integration.

Summation of Signal Inputs

When MOC neurons received repeated excitatory signals, the summation of these inputs led to action potentials, or spikes. These spikes correspond to the firing of the MOC neurons, and researchers were able to measure how stimulation frequency influenced the likelihood and timing of these spikes. More rapid stimulation increased the chances of MOC neurons firing.

The Role of Inhibition

Blocking inhibitory signals during experiments revealed that inhibition plays a vital role in regulating MOC neuron activity. Without inhibitory input, the probability and rate of action potentials increased, indicating that inhibition helps maintain a balance in how MOC neurons respond to incoming sounds.

Computational Modeling Insights

The computational model of MOC neurons provided significant insights into how these cells integrate excitatory and inhibitory inputs. This model mimicked the biologically relevant synaptic activity observed in the experimental setting and allowed researchers to test various scenarios of E-I timing.

Implications for Auditory Processing

The findings from these studies have important implications for understanding how the brain processes sound. By shedding light on the complex interactions of excitatory and inhibitory circuits, researchers can begin to grasp how the auditory system allows us to detect and focus on important sounds amidst noise.

Conclusion

The auditory system is a finely tuned mechanism wherein neurons communicate through a web of excitatory and inhibitory connections. Understanding how these processes work-especially in the context of cochlear amplification and the role of medial olivocochlear neurons-can offer insights into auditory function and potential treatments for hearing disorders. The ongoing research in this area continues to contribute to our broader understanding of how we perceive sound.

Original Source

Title: Fast inhibition slows and desynchronizes auditory efferent neuron activity

Abstract: The encoding of acoustic stimuli requires precise neuron timing. Auditory neurons in the cochlear nucleus (CN) and brainstem are well-suited for accurate analysis of fast acoustic signals, given their physiological specializations of fast membrane time constants, fast axonal conduction, and reliable synaptic transmission. The medial olivocochlear (MOC) neurons that provide efferent inhibition of the cochlea reside in the ventral brainstem and participate in these fast neural circuits. However, their modulation of cochlear function occurs over time scales of a slower nature. This suggests the presence of mechanisms that restrict MOC inhibition of cochlear function. To determine how monaural excitatory and inhibitory synaptic inputs integrate to affect the timing of MOC neuron activity, we developed a novel in vitro slice preparation ( wedge-slice). The wedge-slice maintains the ascending auditory nerve root, the entire CN and projecting axons, while preserving the ability to perform visually guided patch-clamp electrophysiology recordings from genetically identified MOC neurons. The in vivo-like timing of the wedge-slice demonstrates that the inhibitory pathway accelerates relative to the excitatory pathway when the ascending circuit is intact, and the CN portion of the inhibitory circuit is precise enough to compensate for reduced precision in later synapses. When combined with machine learning PSC analysis and computational modeling, we demonstrate a larger suppression of MOC neuron activity when the inhibition occurs with in vivo-like timing. This delay of MOC activity may ensure that the MOC system is only engaged by sustained background sounds, preventing a maladaptive hyper-suppression of cochlear activity. Significance StatementAuditory brainstem neurons are specialized for speed and fidelity to encode rapid features of sound. Extremely fast inhibition contributes to precise brainstem sound encoding. This circuit also projects to medial olivocochlear (MOC) efferent neurons that suppress cochlear function to enhance detection of signals in background sound. Using a novel brain slice preparation with intact ascending circuitry, we show that inhibition of MOC neurons can also be extremely fast, with the speed of the circuit localized to the cochlear nucleus. In contrast with the enhancement of precision afforded by fast inhibition in other brainstem auditory circuits, inhibition to MOC neurons instead has a variable onset that delays and desynchronizes activity, thus reducing precision for a slow, sustained response to background sounds.

Authors: Catherine Weisz, M. Fischl, A. Pederson, R. Voglewede, H. Cheng, J. Drew, L. Torres Cadenas

Last Update: 2024-01-23 00:00:00

Language: English

Source URL: https://www.biorxiv.org/content/10.1101/2023.12.21.572886

Source PDF: https://www.biorxiv.org/content/10.1101/2023.12.21.572886.full.pdf

Licence: https://creativecommons.org/publicdomain/zero/1.0/

Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.

Thank you to biorxiv for use of its open access interoperability.

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