Researchers Discover Brain Circuits Enabling Hearing Develop Without Sensory Experience

Two research teams at the Zilkha Neurogenetic Institute (ZNI) found that before an animal model had any hearing experience, the brain’s elementary thalamocortical circuits with balanced excitation and inhibition functions – a feature of brain activity essential for normal functions — had already formed.

“The scientific view had been that sensory experience should play an instructive role in the initial formation of appropriate brain circuits, so this is a big surprise,” said Li Zhang, assistant professor of Physiology and Biophysics at the Keck School of Medicine, researcher at ZNI and principal investigator on the study. “Because the circuits had already formed, no sensory experience was required.”

With an eye toward future medical advances, the study is a step in addressing a major debate in neuroscience over the last century: What are the roles of genetics and environment in the development of the human nervous system?

“In general we know that both factors play essential roles in the establishment of neural circuits,” said Zhang. “The question is which factor plays a dominant role in the different stages of development, and how. It’s a difficult question to resolve because of the dauntingly complex structure of the brain.”

Their second finding is about how the circuits change during development. They found that after the onset of hearing an elegant refinement of the neuron’s excitation function takes place.

“Previously, it was thought that a pruning of profuse connectivity was responsible for the sharpening of sensory receptive fields of neurons, which leads to improved sensory processing during development,” said Zhang. “We now see that the sharpening depends more on fine adjustments in the strength of excitatory neural connections, and that modulations of the excitatory and inhibitory connections lead to a slight breakdown of the priorly formed excitation–inhibition balance.”

Key to these findings, Zhang said, was a new method of studying the functional neural circuitry of the brain. In the experimental setting, the researchers surgically exposed the cortex of the brain of a young anesthetized rat. They used glass microelectrodes to reach and patch onto neurons buried in the cortical tissue, and then break into their membranes in order to monitor their electrical activity. That allowed the researchers to separately record the inhibition and excitation functions of the neurons.

“This is the first time anyone has applied this cutting-edge electrophysiological technique – in vivo whole-cell voltage-clamp recording – to the developing cortex of the brain,” Zhang said. “Previous hypotheses were limited by techniques that couldn’t reveal detailed structure and subtle changes.”

One research team was led by Zhang, and the other was led by Huizhong W. Tao, an assistant professor in the Department of Cell and Neurobiology at the Keck School.

Currently, Zhang’s research team is examining how the neural circuitry is affected when animals are exposed to noise. “One potential extension of this research line is in looking at how environmental factors play a role in further sculpting the circuits during later development,” he said. In the future, he noted, such research may open the door to insights about the cause of disorders such as autism, in which it is speculated that the auditory system is a major target.