- Email: [email protected]
Yang Dan
Neuron
Q&A Yang Dan Yang Dan is a multifaceted neuroscientist currently working on the neural bases of sleep. In an interview with Neuron, she discusses her upbringing and training as a physicist in China and her hopes for the development of tools that would allow the manipulation of the human brain for therapeutic purposes. Yang Dan is a Paul Licht Distinguished Professor in Biology and an Investigator of the Howard Hughes Medical Institute at the University of California, Berkeley. She grew up in Beijing and studied physics as an undergraduate student at Peking University. She conducted her PhD research in the lab of Mu-ming Poo at Columbia University, where she studied the cellular mechanisms of synaptic transmission and plasticity. For postdoctoral training, she studied visual processing with Clay Reid, Joseph Atick, and Torsten Wiesel at Rockefeller University and Harvard Medical School. Her lab at UC Berkeley uses a variety of techniques, including electrophysiology, imaging, and optogenetics, to study neuromodulation of global brain states and the microcircuits underlying cortical computation. Currently, a major interest of her group is to identify the key neural circuits generating both rapid-eye-movement (REM) sleep and non-REM sleep. To understand cognitive control of goal-directed behavior, her lab is also investigating how the prefrontal cortex generates taskrelated activity and how such activity modulates the downstream targets for optimal behavioral control. What do you think are the big questions to be answered next in your field? In the last few years I have been most obsessed about the neuroscience of sleep. There are two general questions. The first is what mechanisms control sleep. A key challenge in my view is that neurons with different functions (e.g., some neurons enhance sleep, others enhance wakefulness) are often spatially intermingled, making it difficult to target a functionally homogeneous group of neurons for manipulation and circuit analysis. This is not just limited to the sleep circuit; the physical proximity of neurons with heterogeneous functional properties poses a
during sleep or if it is a single process that is fundamental to all of them.
Yang Dan Howard Hughes Medical Institute and the University of California, Berkeley
general challenge for understanding the neural circuits underlying many types of behavior. But once we figure out how to target a group of neurons playing the same functional role, perhaps by finding specific genetic markers or using other tricks, we will have a lot of powerful tools to figure out their inputs and outputs. Given the amazing technological advances in recent years, I think solving the circuit for sleep control is just a matter of time. The other question is what is sleep for. I think this is a harder question. There are different ideas out there, related to general repair and restoration or specific mental functions such as memory consolidation. Sleep is probably important for all of them, as shown by the effects of sleep deprivation, but we don’t know whether these diverse functions are mediated by multiple processes occurring in parallel
To tackle your favorite research question, is there a tool that either needs to be developed or is currently available that could be implemented in a novel way? Most of us use model organisms to study the neural circuits underlying behavior. For example, my lab uses the mouse to study sleep, and a variety of viral tools can be used in conjunction with mouse genetics to target specific cell types for manipulation and circuit analysis. Unfortunately these techniques are not applicable to humans because of their invasive nature. I would like to see the development of safe methods for targeting and manipulating specific cell types in the human brain, which will greatly facilitate the translation of our research findings in animal models to clinical applications. For example, we have found several types of neurons in particular brain regions that can enhance sleep when we optogenetically activate them. I wish there were a way to activate those neurons in my own brain when I am jetlagged and struggling to fall asleep. Who were your key early influences? Albert Einstein, Marie Curie, and my dad. When I was a child, China was quite poor and not yet opened to the west, but great scientists were held in high esteem by the public. In our residential compound where most people worked in the same institute as my dad, if you asked the kids about their role models, they would probably name some scientists rather than movie stars. Of course we did not understand their science until much later, but we often heard stories about people like Albert Einstein and Madame Curie, and we thought that scientists were heroic, smart, and really cool people. Neuron 91, September 21, 2016
1195
Neuron
Q&A My dad, who is a physicist, taught me a lot of math and introduced me to books early on. So before I went to elementary school I was already reading a lot and showing off my ability to solve math problems to older kids. This gave me an important head start, and once I realized that I was good at something it was natural for me to be interested in that subject and spend more time on it. Later, throughout my school years and research career, there were also many wonderful teachers and mentors who took great interest in me and urged me on to push the limits and realize my potential. What’s your favorite experiment? Always the ones we are doing at the moment. Each morning I open my eyes, and my first thought is which experiment might generate the first piece of data today. I can’t wait to go to the lab so I can look at the result and talk to people about it. What motivated you to become a scientist? I wanted to be a scientist long before I knew what it’s like to be a scientist, because of the stories about scientists that I heard as a child, which are probably romanticized versions of reality. Now I know about all the challenges, but if I had to do it all over again I would not choose any other profession. We are given the freedom to work on the problems that interest us, to follow our curiosity—we are paid to play. I also enjoy the opportunity to interact with so many smart, stimulating people.
What is your view on big datagathering collaborations as opposed to hypothesis-driven research by small groups? Obviously both are important and they have crucial parts to play in neuroscience. People with different temperaments might be better suited for one or the other, and each of us needs to figure out which setting allows us to make the most of our own talent. How do you view the level of crosstalk between disciplines, for example physics, mathematics, engineering, humanities, and social sciences? I think it is essential. It’s not only the specific skill sets that different people bring, but also different ways of thinking and approaching a given problem. I studied physics as an undergraduate student with no background in biology, but after I struggled through the first few years of graduate school, I noticed that my way of thinking was a little different from my peers, which could be an advantage. When people with different perspectives come together, it can really spark innovative ideas. What advice do you find yourself giving to your students and postdocs? Have the courage to change fields if you see an exciting opportunity for someone with your skill set to make a real difference. But be thoughtful and strategic about it. I have personally changed quite a few times, studying
pure physics as an undergraduate student in China and moving to the U.S. to study neurobiology, which I knew nothing about except that I wanted to find out how the brain works. Within neuroscience, I went from synaptic functions at the cellular level to visual processing at the circuit level to my recent interests in sleep and the prefrontal cortex. The switch was never easy, but in my case the payoff was always worth it. What question keeps you awake at night? It is ironic—I lose a lot of sleep thinking about how our brain goes to sleep, what circuits control sleep, and what causes us to lose sleep. What do you do when you’re not in the lab? I travel to many parts of the world to attend scientific meetings, which is really a great perk of being a scientist. I am also a fanatic about physical exercise. I used to do a lot of dance workouts, but now I have less time so I just use the elliptical machine at home and take long walks when I visit new places. What career paths did you consider other than a scientist? The first time I saw a ballet as a little girl I wanted to be a ballerina, and I destroyed quite a few pairs of shoes trying to stand en pointe. I think my parents were very relieved when my interest in being a scientist took over. http://dx.doi.org/10.1016/j.neuron.2016.08.039
1196 Neuron 91, September 21, 2016
Q&A Yang Dan Yang Dan is a multifaceted neuroscientist currently working on the neural bases of sleep. In an interview with Neuron, she discusses her upbringing and training as a physicist in China and her hopes for the development of tools that would allow the manipulation of the human brain for therapeutic purposes. Yang Dan is a Paul Licht Distinguished Professor in Biology and an Investigator of the Howard Hughes Medical Institute at the University of California, Berkeley. She grew up in Beijing and studied physics as an undergraduate student at Peking University. She conducted her PhD research in the lab of Mu-ming Poo at Columbia University, where she studied the cellular mechanisms of synaptic transmission and plasticity. For postdoctoral training, she studied visual processing with Clay Reid, Joseph Atick, and Torsten Wiesel at Rockefeller University and Harvard Medical School. Her lab at UC Berkeley uses a variety of techniques, including electrophysiology, imaging, and optogenetics, to study neuromodulation of global brain states and the microcircuits underlying cortical computation. Currently, a major interest of her group is to identify the key neural circuits generating both rapid-eye-movement (REM) sleep and non-REM sleep. To understand cognitive control of goal-directed behavior, her lab is also investigating how the prefrontal cortex generates taskrelated activity and how such activity modulates the downstream targets for optimal behavioral control. What do you think are the big questions to be answered next in your field? In the last few years I have been most obsessed about the neuroscience of sleep. There are two general questions. The first is what mechanisms control sleep. A key challenge in my view is that neurons with different functions (e.g., some neurons enhance sleep, others enhance wakefulness) are often spatially intermingled, making it difficult to target a functionally homogeneous group of neurons for manipulation and circuit analysis. This is not just limited to the sleep circuit; the physical proximity of neurons with heterogeneous functional properties poses a
during sleep or if it is a single process that is fundamental to all of them.
Yang Dan Howard Hughes Medical Institute and the University of California, Berkeley
general challenge for understanding the neural circuits underlying many types of behavior. But once we figure out how to target a group of neurons playing the same functional role, perhaps by finding specific genetic markers or using other tricks, we will have a lot of powerful tools to figure out their inputs and outputs. Given the amazing technological advances in recent years, I think solving the circuit for sleep control is just a matter of time. The other question is what is sleep for. I think this is a harder question. There are different ideas out there, related to general repair and restoration or specific mental functions such as memory consolidation. Sleep is probably important for all of them, as shown by the effects of sleep deprivation, but we don’t know whether these diverse functions are mediated by multiple processes occurring in parallel
To tackle your favorite research question, is there a tool that either needs to be developed or is currently available that could be implemented in a novel way? Most of us use model organisms to study the neural circuits underlying behavior. For example, my lab uses the mouse to study sleep, and a variety of viral tools can be used in conjunction with mouse genetics to target specific cell types for manipulation and circuit analysis. Unfortunately these techniques are not applicable to humans because of their invasive nature. I would like to see the development of safe methods for targeting and manipulating specific cell types in the human brain, which will greatly facilitate the translation of our research findings in animal models to clinical applications. For example, we have found several types of neurons in particular brain regions that can enhance sleep when we optogenetically activate them. I wish there were a way to activate those neurons in my own brain when I am jetlagged and struggling to fall asleep. Who were your key early influences? Albert Einstein, Marie Curie, and my dad. When I was a child, China was quite poor and not yet opened to the west, but great scientists were held in high esteem by the public. In our residential compound where most people worked in the same institute as my dad, if you asked the kids about their role models, they would probably name some scientists rather than movie stars. Of course we did not understand their science until much later, but we often heard stories about people like Albert Einstein and Madame Curie, and we thought that scientists were heroic, smart, and really cool people. Neuron 91, September 21, 2016
1195
Neuron
Q&A My dad, who is a physicist, taught me a lot of math and introduced me to books early on. So before I went to elementary school I was already reading a lot and showing off my ability to solve math problems to older kids. This gave me an important head start, and once I realized that I was good at something it was natural for me to be interested in that subject and spend more time on it. Later, throughout my school years and research career, there were also many wonderful teachers and mentors who took great interest in me and urged me on to push the limits and realize my potential. What’s your favorite experiment? Always the ones we are doing at the moment. Each morning I open my eyes, and my first thought is which experiment might generate the first piece of data today. I can’t wait to go to the lab so I can look at the result and talk to people about it. What motivated you to become a scientist? I wanted to be a scientist long before I knew what it’s like to be a scientist, because of the stories about scientists that I heard as a child, which are probably romanticized versions of reality. Now I know about all the challenges, but if I had to do it all over again I would not choose any other profession. We are given the freedom to work on the problems that interest us, to follow our curiosity—we are paid to play. I also enjoy the opportunity to interact with so many smart, stimulating people.
What is your view on big datagathering collaborations as opposed to hypothesis-driven research by small groups? Obviously both are important and they have crucial parts to play in neuroscience. People with different temperaments might be better suited for one or the other, and each of us needs to figure out which setting allows us to make the most of our own talent. How do you view the level of crosstalk between disciplines, for example physics, mathematics, engineering, humanities, and social sciences? I think it is essential. It’s not only the specific skill sets that different people bring, but also different ways of thinking and approaching a given problem. I studied physics as an undergraduate student with no background in biology, but after I struggled through the first few years of graduate school, I noticed that my way of thinking was a little different from my peers, which could be an advantage. When people with different perspectives come together, it can really spark innovative ideas. What advice do you find yourself giving to your students and postdocs? Have the courage to change fields if you see an exciting opportunity for someone with your skill set to make a real difference. But be thoughtful and strategic about it. I have personally changed quite a few times, studying
pure physics as an undergraduate student in China and moving to the U.S. to study neurobiology, which I knew nothing about except that I wanted to find out how the brain works. Within neuroscience, I went from synaptic functions at the cellular level to visual processing at the circuit level to my recent interests in sleep and the prefrontal cortex. The switch was never easy, but in my case the payoff was always worth it. What question keeps you awake at night? It is ironic—I lose a lot of sleep thinking about how our brain goes to sleep, what circuits control sleep, and what causes us to lose sleep. What do you do when you’re not in the lab? I travel to many parts of the world to attend scientific meetings, which is really a great perk of being a scientist. I am also a fanatic about physical exercise. I used to do a lot of dance workouts, but now I have less time so I just use the elliptical machine at home and take long walks when I visit new places. What career paths did you consider other than a scientist? The first time I saw a ballet as a little girl I wanted to be a ballerina, and I destroyed quite a few pairs of shoes trying to stand en pointe. I think my parents were very relieved when my interest in being a scientist took over. http://dx.doi.org/10.1016/j.neuron.2016.08.039
1196 Neuron 91, September 21, 2016