Clues to How the Auditory Cortex Controls Subcortical Circuits

By Hannah Oberle and Pierre Apostolides, Ph.D.

Undergraduate textbooks typically paint the central auditory system as a linear, hierarchical structure: Sound information enters the brain via the 8th nerve, and electrical signals ascend through subcortical auditory circuits in a “bucket brigade” fashion. Sound is processed along each step of the pathway, and the auditory information reaches the auditory cortex, which supports higher-order perception and behavior.

However, this textbook model is somewhat simplistic: Decades of research show that the auditory cortex originates descending projections that operate in parallel with the ascending auditory system: Neurons in the deep layers of auditory cortex send excitatory nerve fibers back down to the majority of subcortical regions, like the thalamus, inferior colliculus, and cochlear nucleus. 

This image shows an example micrograph of an injection site in the left auditory cortex in the mouse model. Dashed lines denote approximate borders of auditory cortical areas. Credit: Oberle et al./eLife

These “corticofugal” projections likely play a major role in hearing, as they provide an avenue for higher-order signals from the auditory cortex to shape how the early auditory system interprets incoming sounds from the ear. This cortical input conveys “top-down” information, which may provide contextual information to local processing in subcortical regions.

Despite the existence of corticofugal pathways being well established, little is known regarding the cellular and biophysical mechanisms that enable the auditory cortex to transmit top-down signals. In addition, we don’t understand how descending cortical signals are integrated with ascending information.

In our eLife paper published in January 2022, we addressed this knowledge gap by studying the descending projection from the auditory cortex to the inferior colliculus (IC), a midbrain hub important for sound localization and speech perception. We combined optogenetic approaches with in vivo and in vitro patch-clamp electrophysiology in mice to study how the auditory cortex transmits messages to the IC.

Our results revealed surprising biophysical properties of auditory cortex -> IC synapses that allow descending cortical signals to quickly amplify how individual IC neurons respond to ascending sound information. Interestingly, descending cortical pathways are not unique to the auditory system but are also a feature of the brain’s visual, tactile, and olfactory pathways. Thus, our results may provide broadly generalizable insight into how the mammalian brain dynamically processes incoming sensory information.

Pierre Apostolides PhD

A 2019 Emerging Research Grants scientist, Pierre Apostolides, Ph.D., is an assistant professor of otolaryngology-head and neck surgery at the University of Michigan's Kresge Hearing Research Institute. Neuroscience graduate student Hannah Oberle is a member of the Apostolides Lab. Apostolides is also an assistant professor of molecular and integrative physiology at the University of Michigan Medical School.


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