If we want to understand how the brain develops and learns, neuroscientist Dr. Hyungbae Kwon sees we have to look at the scale of interacting circuits. To do so, Hyungbae's lab at Max Planck Florida (the lab's moving to Johns Hopkins University in 2019) explores the way experience affects neural circuits using state-of-the-art tools, like optogenetics and in vivo calcium imaging with Inscopix miniscopes.
We had the privilege to learn more about what motivates his research, and his experience working with our field scientific consultants who got his Inscopix miniscope experiments up and running in the first animal!
You can catch Hyungbae speaking at the Max Planck Florida Sunposium in March!
What does your group study?
My lab focuses on three main topics. First, we want to understand the cellular logic that drives neurons to make a right connection. This process is generally regulated by genetically programmed intrinsic mechanisms and further shaped by neuronal activity. Especially, I want to understand activity-dependent components of synapse formation. The second topic I am interested in is to develop a new method for neuroscience. It could be a novel synthetic biosensor or a new imaging technique. Basically, the new direction will be a way to make people see neuronal structure or activity better, and change animal’s behavior/perception/memory in a controllable manner. Lastly, we are trying to understand cellular mechanisms of cognitive learning. This will be distinguished from the typical cue-driven associative learning. For example, every day we interact with other people and explore in a given environment, and we learn a lot of things without having specific rewards. These types of surrounding stimuli constantly stimulate neurons and perhaps accumulated in a specific form of learning in the brain. My lab wants to tease out what this form is.
In the past these studies have been conducted at the Max Planck Florida Institute for Neuroscience, but my lab will be moving to join the Neuroscience Department at Johns Hopkins in summer 2019.
Although your formal training is as a cell biologist, you've incorporated several circuit neuroscience techniques into your lab. What is your favorite circuit neuroscience technique?
Gaining circuit level understanding requires experimental cross-examination in several ways. Among them, I like optogenetic methods that allow us to examine functions of specific circuits. I also like various imaging techniques like Inscopix miniature microscope imaging or two-photon imaging that show neural correlates of animal behavior in real-time. Two-photon microscopy is really powerful to visualize neuronal activity at cellular or even synapse resolution, but does not allow imaging of deep brain structures or neuronal activity in freely behaving animals as the Inscopix miniscope does.
The reason I got interested in the circuit level study is simple. Because I want to understand how learning is represented at a large scale. While I was looking at dendritic spines, I was able to define basic principles underlying synapse formation/plasticity, but the overall shape of learning or memory will not be visualized. By having circuit level techniques, I can examine neuronal changes in multiple ways, which will provide a more complete understanding.
What was your first “flashing neurons” moment using Inscopix technology?
Obviously, the first “Wow” moment was to see Ca2+ responses from individual neurons in behaving animals. Even though we had no experience in miniscope imaging before, a field scientific consultant from Inscopix, Patrick Stemkowski, visited our lab and made all the processes move smoothly. We even got the cool imaging from the very first animal! My postdoc Kanghoon got recordings from several individual neurons after the first round of implants in the medial shell of the nucleus accumbens.
The most impressive part is that Inscopix really tried to make our experiments work as we wanted. It was not like shipping a package and saying good luck. Inscopix’s scientific support system really saved us time and that’s something different from other companies.
You were recently awarded the 2018 NIH Director’s Pioneer Award. Congratulations! Could you describe the new direction you're taking the group with this award?
The goal of this project is to visualize the action of neuromodulation at a cellular resolution. However, more broadly, when I wrote the proposal, I had one question in mind. “How can I visualize feelings or emotions?”
Artists express “Sadness” or “Happiness” by drawing or making sculptures. We normally express our feelings by facial expression and language. But, when people say, “I am sad”, the expression is very ambiguous. You can be sad because your mom is sick or you lost a job. In both cases, people say the same sentence “I am sad”, but the meaning of sadness is different. Thus, just by listening “I am sad”, there is no way to understand exact feelings. Moreover, there is no way to express exactly what your feeling is. It could be combination of several feelings. To me, almost nothing is known about these kinds of questions. In extreme cases, maybe the origin of sadness and happiness is the same. No one knows. Language will never be enough to express complex feelings or emotions.
My ultimate goal is to show these feelings or emotions by individual cells. By doing so, it may be possible to quantify our emotions in the future. To begin with we developed novel optogenetic techniques named Cal-Light and iTango2, which label active neuronal populations and neuromodulator-sensitive populations, respectively. By having these techniques, we can narrow down marking a specific subset of neurons at the moment animals are behaving or feeling. Our technique is still far from doing this, but my research will move toward this direction.
What is the best piece of career advice you have ever been given?
When I first moved to Harvard to do postdoctoral research, I was overwhelmed by the atmosphere. There were too many smart people and they were extremely productive. This overwhelming environment made me feel really small, and my self-confidence hit the bottom. I was frightened by a fact that I had to compete with these people for the same job. Fortunately, my postdoc mentor, Bernardo Sabatini, changed my mind. He treated me very respectfully and always encouraged me even if I showed him stupid things. At that time, I had the following quote at the bottom of my email credential. “The way you see them is the way you treat them, and the way you treat them is the way they often become”. Exactly like this quote, Bernardo really held me in high regard, and showed it in the way he treated me, and magically my fearful mind was gone.
What do you enjoy doing outside of the lab?
I play ping pong every day after lunch. This might be the best part of day and doing regular exercise gets rid of stress. Outside of the lab, I am not sure who would dare think of doing something else with three kids!