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February 4, 2023

Sounds affect cortical wiring early in life, study finds

By PETER NOVELLO | March 11, 2021



The researchers studied the influence of early peripheral activity on the connectivity of the auditory cortex. 

Sound has more power in shaping the intricate connections in the brain than we may realize. 

The influence of sensory stimuli in the development of cortical circuits and its associated functions is the subject of a recently published research paper, titled “Early peripheral activity alters nascent subplate circuits in the auditory cortex.” This investigation into the impact of sound activity on the development of the auditory cortex was conducted by Xiangying Meng, Didhiti Mukherjee, Joseph P. Y. Kao and Patrick O. Kanold. 

In their paper, the researchers explain the science behind cortical development and the ways in which their discoveries broaden the previously defined influence of sensory stimuli on the interactions of neurons in the brain. 

Thalamocortical (TC) axons are known to initially target subplate neurons (SPNs) before maturing and eventually innervating neurons in layer 4 (L4). Investigators primarily focus on L4 neurons when examining the role of early sensory experiences in sensory systems. SPNs are responsible for the development of TC axons and intracortical circuits. Early removal or modification of SPNs has been linked to the onset of neurodevelopmental disorders. 

The researchers hypothesized that inducing early peripheral spontaneous and sound-generated activity can allow for the early maturation of SPNs present in the auditory cortex, preceding the prevalence of the TC and L4 interactions. 

In an interview with The News-Letter, Kanold, the corresponding author and a Hopkins Biomedical Engineering professor, explained his team’s approach to understanding circuit development in mice.

“You need to understand the system you're working in,” he said. “We spent a lot of time looking at baseline circuit development to understand the auditory cortex of mice.”

However, the methodologies used to explore the trillions of connections in the brain also present limitations, especially when researching the inner parts of the brain.

“These neurons we are studying are very deep in the brain and have been traditionally ignored,” Kanold said. “[Current] methodologies do not work deep in the brain.”

A method to constantly monitor cortical development would be ideal, Kanold noted. Such a method would help in conducting similar research projects in the future. 

Despite the limitations, Kanold and his colleagues used in vivo imaging techniques to analyze the spontaneous and sound-evoked activity present in the auditory cortex of mice under various conditions. Additionally, they developed in vitro recordings of parts of the brain to further examine the functions of the cortical circuits. For example, they investigated the functions of cortical circuits present in deaf mice.

In another set of experiments, the researchers placed mice in either a silent chamber or a chamber filled with ambient noises. In the noisy chamber, they incrementally presented different tones. Then, they gauged if the presence of external sounds during the neonatal stage causes changes in SPN circuits. They found that it did: The mice that were placed in the noisy chamber were observed to have greater circuit diversity and higher amplitudes among the excitatory and inhibitory inputs.

The study’s results suggest that sensory stimuli influence the development of the auditory cortex and the cortical circuits. Compared to mice observed in the noisy colony, those raised in silence possessed different SPN circuits. The mice exposed to a range of sounds had synaptically active circuits. Thus, Kanold and his colleagues concluded that it is evident that SPN circuits can be modified by peripheral activity. 

Kanold described how his team’s findings expand previously accepted notions of the effects of sensory stimuli on the cortex after TC axons innervate L4.

“[We] are building a sketch or layout to be elaborated upon later... [that] can change the capacity of plasticity,” he said. 

The investigation’s findings also have significant scientific and medical applications. Hearing loss in infants can be clarified by examining circuit compositions, potentially allowing physicians to diagnose deafness in utero. Kanold suggested that there is a need to understand the impact of early sensory experience in diagnosing hearing loss and studying circuit function in the auditory cortex. 

“Early experiences can leave a trace,” Kanold said. “Something happening very early, such as humans in the womb, can affect brain wiring. At birth, we are not a blank slate. We had experience.”

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