By Michael T. Roberts, Ph.D.

Most of our auditory experience requires extensive and precise computations in the brain. While the neural circuitry underlying these computations has become increasingly clear over the past several decades, there has remained a big gap in our understanding of the neural circuitry in an important brain region called the inferior colliculus (IC).

Located in the midbrain, the IC is the hub of the brain’s auditory pathway. Like an airport hub that processes travelers moving among farflung airports, the IC receives and processes most of the output of lower auditory centers and provides the major source of auditory input to higher brain centers.

Although the IC plays important roles in most auditory functions, including speech processing and sound localization, it has proven difficult to identify the types of neurons (nerve cells) that make up the IC. This has hampered progress because the ability to identify neuron types is a prerequisite for determining how specific neurons interconnect and function within the broader auditory circuitry.

Recently, my lab at the University of Michigan tackled this long-standing problem and successfully identified a novel neuron type called VIP neurons. VIP neurons make a small protein called vasoactive intestinal peptide. Despite its name, previous studies have shown that VIP is made by specific types of neurons in several other brain regions.

Our team, led by postdoctoral fellow David Goyer, Ph.D., hypothesized that VIP is a marker for a class of neurons in the IC. To test this hypothesis, we used a genetically engineered mouse to label VIP neurons with a red fluorescent protein. This made it possible to use fluorescence microscopy to target experiments to VIP neurons in the IC.

These experiments revealed that VIP neurons in the IC have internally consistent anatomical and physiological features, supporting the conclusion that IC VIP neurons constitute a distinct neuron type. Examination of the neuronal processes of VIP neurons further revealed that individual VIP neurons likely receive input from a range of sound frequencies. Work by collaborators in the Schofield Lab at Northeast Ohio Medical University showed that VIP neurons also send output to several brain regions, including to higher and lower auditory centers and to a brain region involved in visual processing.

In another set of experiments, we combined electrical recordings from VIP neurons with a technique called optogenetics, which allows scientists to stimulate specific populations of neurons using brief flashes of light. These experiments revealed that VIP neurons receive input from the dorsal cochlear nucleus, one of the first brain regions in the auditory pathway. The path from the cochlea to VIP neurons is therefore quite short, passing through only three synapses.

This study, which combined both sets of experiments and was published in eLife on April 18, 2019, showed that VIP neurons are a distinct and readily identifiable class of IC neurons. Based on their features, we hypothesize that VIP neurons play a broadly influential role in sound processing. We and the Schofield lab are currently testing this hypothesis, with a particular emphasis on determining how VIP neurons contribute to speech processing in the IC. 

A 2017 Emerging Research Grants scientist, Michael T. Roberts, Ph.D., heads the Roberts Laboratory and is an assistant professor at the Kresge Hearing Research Institute, University of Michigan.

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