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Your lab’s most recent work, published in Nature, details a very fundamental discovery in the inner ear. Why is this research important?
FUCHS: For the first time, we managed to measure and record the elusive electrical activity of the type II neurons in the snail-shell-like structure called the cochlea. And it turns out these cells do indeed carry signals from the ear to the brain. The sounds they likely respond to would need to be loud, such as sirens or alarms; sounds that might be even be described as painful or traumatic.
Would you describe the methodology?
FUCHS: Working with week-old rats, neuroscience graduate student Catherine Weisz removed live, soft tissue from the fragile cochlea and, guided by a powerful microscope, touched electrodes to the tiny type II nerve endings beneath the sensory hair cells. Different types of stimuli were used to activate sensory hair cells, allowing her to record and analyze the resulting signals in type II fibers.
This research really resonates?
FUCHS: Yes, it isn’t often that one answers a question that’s been circulating around for this long. We’ve known about these neurons anatomically for a long time, a half a century or better. And finally we know something about their functionality, and that’s pretty exciting.
How did you come to contemplate this 50-year-old question?
FUCHS: This arose from an interaction with Dr. Xinzhong Dong in the Neuroscience department, and a fellow member of the Center for Sensory Biology. He studies small diameter afferent neurons in the somatosensory system of mice by getting them to express fluorescent proteins. We looked in the cochlea of some of these animals and thought the type II afferents might be labeled. It’s not yet certain whether that is correct, but it inspired Cat Weisz to attempt to record from these neurons. Her efforts were very much facilitated by the fact that Dr. Elisabeth Glowatzki, Cat’s other thesis mentor, had previously devised techniques for recording from very small neurons in the cochlea.
What motivated you to study the inner ear in the first place?
FUCHS: I trained as a synaptic physiologist. Even my undergraduate work at Reed College (in Portland, Oregon) had some neurobiology in it. Then I went to Stanford for my doctorate where I looked at the way in which synapses work in the crayfish. Eventually I wound up in England for post doctoral work with Robert Fettiplace who studies the ear. It was at that point in 1981 that I began working on the ear, but primarily as a model of interesting synaptic physiology.
I then got my first job at the University of Colorado in the physiology department where I continued to do experiments on hair cells and synapses. Gradually I realized that although I’m a synaptic physiologist, I was in fact working in the ear, and so should be in a hearing group somewhere. Eventually, the opportunity arose for a position here with the Center for Hearing and Balance. That’s when I joined an established hearing group and became firmly identified as a hearing scientist. Our lab continues to work on afferent and efferent synaptic connectivity of the inner ear.
Let’s back up a bit. Define “synaptic physiologist.”
FUCHS: The short answer: Electrode jockey! The long answer: we call ourselves synaptic physiologists, because we study the communication between cells that occurs at synapses – those contact points between two cells across which information flows. In the nervous system, that term specifically means there is some kind of information transfer across that contact. It was one of the big advances in cell biology when people recognized there was in fact actually a little gap between two cells at that contact point. That was a topic of much argument in the early days of neuro-anatomy, as to whether cells really were separated by any extracellular space.
The kinds of chemical synapses that I study involve one cell, which we will call pre-synaptic, having a signal that propagates electrically and gives rise to the release of a chemical that then drifts across the intervening little space and then binds to molecular receptors for that chemical on the post-synaptic cell. The nervous system does this weird thing: There’s an electrical signal on one neuron which gets transformed into a chemical signal at the synapse and that inspires an electrical signal in the second neuron on the other side of the synapse. Chemicals are used to go from cell to cell, but within one cell, it’s an electrical signal that propagates. That’s fortunate for us, because many of the drugs we use to treat nervous system disorders have to do with what kinds of chemicals are released, what kinds of molecules those chemicals bind to, and what are the downstream signaling pathways. We are interested in establishing these same facts for the ear.
How does this add to what we know about the neuro-pharmacology of the inner ear?
FUCHS: Now we have the chance to think about defined scenarios, such as, if this specific chemical is being released and that particular molecular receptor is being activated, then what drugs act on those kinds of signals? We’ve first got to know what chemicals are there and what molecular receptors are there before we can devise any rational strategies for pharmacotherapeutics.
Type II afferents, whatever they’re doing, we now know something about the way they do it. We know they respond to glutamate and ATP. Our lab is beginning to characterize the molecular receptors functionally. That will lead us to ways of characterizing them genetically and then we can begin to think about pharmacotherapeutics.
You’re clearly delighted about the discovery.
FUCHS: I have to say that in my career this is one of the most efficient productions of a scientific paper that I’ve ever been a participant in: For all this to happen in one year, for a graduate student (Catherine Weisz) working on her first project, that is quite a feat. Quite a remarkable feat!
Paul Fuchs on how being a scientist is like being an explorer