By Hannah Oberle and Pierre Apostolides, Ph.D.
The central auditory system is classically thought of as an ascending system, where acoustic information is processed across a step-by-step hierarchy of increasingly complex circuits. However, this model is simplistic because we know that higher order brain regions such as the auditory cortex also send descending projections back to “lower” circuits.
These descending projections might provide “feedback” signals that shape how early brain regions process sound information. However, a major knowledge gap is that we know little regarding the physiology of descending auditory pathways.
The inferior colliculus (IC) is an auditory midbrain region important for speech processing, and a major target of such descending projections. Excitatory axons from a higher order brain region, the auditory cortex, primarily target the subregion of the IC known as the shell. These descending projections enable the auditory cortex to transmit complex “high-level” feedback signals that shape early sound processing in the IC.
This micrograph from the Journal of Neuroscience publication shows the mouse inferior colliculus. Panel C displays a magnified look at the dorsomedial shell, indicated by the dashed rectangle in panel B. The red fluorescent labeling allowed the experimenters to make electrophysiology recordings from either inhibitory or excitatory neurons. Credit: Oberle et al./Journal of Neuroscience
Interestingly, many previous studies over the past several decades showed that activity in the auditory cortex inhibits IC neurons and refine how the local neurons respond to different sound features. This result is quite surprising and seems paradoxical, as the descending projections from the auditory cortex that target the IC are excitatory.
Furthermore, these excitatory neurons from the auditory cortex are thought to primarily target other excitatory neurons in the IC. If the existing circuit is known to be excitatory, how can the auditory cortex have an inhibitory effect on IC neurons?
In this work published in Journal of Neuroscience in June 2023, we focused on understanding how descending auditory cortical projections can generate inhibition at the dorsomedial region of the shell IC. To study this, we used slice electrophysiology to record the electrical signals from neurons. We determined how neurons from the auditory cortex drive activity in the IC by applying an approach called optogenetics.
Via this method, we can stimulate descending auditory cortical axons by activating light-sensitive channels via blue light. We were also able to target our electrophysiology recordings to either inhibitory or excitatory neurons in the IC using a fluorescent marker, thereby enabling us to directly compare how these two different groups of neurons respond to auditory cortex activity.
The results from these experiments first confirmed that auditory cortex projections preferentially contact excitatory IC neurons, and that auditory cortical activity can drive spikes in a subset of these excitatory IC neurons.
However, we also found that excitatory IC neurons contact neighboring inhibitory IC neurons. Consequently, when the auditory cortex drives spikes in excitatory IC neurons, they “relay” these signals to the inhibitory IC neurons, who in turn also fire spikes. These inhibitory IC neurons then generate inhibition within the local circuit.
This multisynaptic cascade thus provides a mechanistic explanation for how excitatory projections from the auditory cortex generate inhibition in the IC.
Neuroscience graduate student Hannah Oberle is a member of the Apostolides Lab. 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. He is also an assistant professor of molecular and integrative physiology at the University of Michigan Medical School.
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