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Meet the Community: Florian Engert
Interview by Charlie Schmidt
Q: How did you become interested in neuroscience? A: My background is in physics–that was my undergraduate major while I was at school in Germany. There were many opportunities, as there are now, in neuroscience for people with a quantitative background. There was a market for that. So, I did a one-year stint in neuroscience as an undergrad and that's when I got hooked. What interested me most is how the brain changes when you experience something, which relates directly to learning and memory, which is what I work on now. Q: How would you describe the emphasis on neuroscience research at MCB? A: It's one of the most vibrant and exciting fields being studied at MCB. Until about 10 years ago, John Dowling was one of the very few doing neuroscience here. But now several more faculty members are involved: Catherine Dulac, Markus Meister, Samuel Kunes, Venkatesh Murthy, me, and now Joshua Sanes and Jeff Lichtman will be joining us this summer. It's getting boosted even further by the new FAS Center for Brain Science. How the brain works is probably one of the last, great remaining mysteries in science. Q: In your postdoctoral research, you found the brain responds to a stream of impulses by forming new connections for information storage. How did these findings influence the way scientists view the brain? A: It had been hypothesized for a long time that you need to form new connections for memory, but no one could confirm that. We used two-photon microscopy to look carefully at nerve cells and were able to see the growth of new synapses in response to certain stimulation paradigms that were known to strengthen synaptic connections. The speed at which they grew was surprising–within five minutes. No one expected that. So, the finding that you can create all these new connections forces one to rethink the brain: it's actually a very dynamic structure. Q: Since coming to Harvard, you've shifted your experimental model from rat slices and tadpoles to zebrafish. Why? A: We're trying to find out how visual information is transformed into a neural code in the brain. We're interested in what the neuronal representation of visual information is and how it develops over time. Zebrafish are an ideal model for these studies because they have a precise and acute visual system. They use vision to hunt for prey and navigation, unlike the tadpole, which relies on odor and smell. Furthermore they are perfectly translucent at the earlier stages during development–which facilitates imaging experiments enormously–and last but not least, fish develop outside of the maternal body, which allows us to study the growth of the nervous system during the critical period when it matures and starts to function as a circuit. So, in zebrafish, we follow the synaptic connections involved in the development of the visual system; beginning with the moment neurons in the eye connected to the brain. We use two-photon microscopy and in vivo patch clamp techniques as our main tools, touching on two key questions: how are electrical signals processed in single neurons? and how is the visual signal processed by whole networks of neurons? Q: That sounds challenging. A: Yes, but we can break up these questions into subtopics that are more manageable. For instance, a specific question deals with how motion is detected. How do individual neurons distinguish leftward motion from rightward motion? Is there anything we can say about this? One thing we've found is that neurons can be trained to become motion detectors–this isn't something that is genetically hardwired; it's an aspect of learning and memory. One question we're testing now is whether individual neurons can be trained to detect any kind of stimulus. Q: Do these findings shed light on how higher organisms, including humans, process learning and memory? A: The advantage is that zebrafish are vertebrates and have, at the neuronal basis, a similar system to humans. They use the same neurotransmitters–like glutamate for excitation, GABA for inhibition–and they also use NMDA receptors for modulation. The other striking similarity is that the activity patterns you need to strengthen or weaken connections are almost identical in tadpoles, zebrafish, and mammals. So, the basic rules seem to be very similar, even if the global morphology is distinctly different. Q: I understand you're developing screens to identify learning mutants in zebrafish. How is this work coming along? A: Yes, we're doing this in parallel–one way to study how the brain deals with information is to perturb the system and see how it changes. One popular technique is to use transgenic fish that lack individual genes or proteins. We're developing assays to test for fish that are unable to learn. The approach is a simple space avoidance assay--we put a fish in a tank, half of which is electrified. Fish learn to stay out of the area where they get shocked; they learn to associate a location in space with a negative sensation. We're still working on the assay to screen for mutants, but we're not quite there yet. The system has to be reliable. We've been relying heavily on John Dowling, who has a huge fish facility here. He's been priceless in terms of his assistance.
A: Markus Meister helps with the theoretical aspects of the research. Venkatesh Murthy in the lab next door helps with all the problems in molecular biology that we have to deal with. And then Catherine Dulac and Sam Kunes help by providing advise and time for discussions. Q: What achievement or aspect of your research are you most proud of? A: I think establishing the zebrafish as a model system for processing visual information. That's something that will probably be valuable for the whole community. Q: Is there any particular message you'd like to get across? A: I like working at Harvard; it's really a great place. I was warned before I came here that it was very competitive and indifferent, but that's entirely untrue. People are extremely helpful and friendly and very collegial. There's a lot if interaction in a lot of good ways. And the students are spectacular–all of them. That's a great advantage of being at Harvard.
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