Kay Tye’s pioneering work with projection-specific optogenetics has built a strong foundation for future insights into healthy and addiction-related behaviors. By understanding the neural circuitry that interprets pleasure and pain, she was able to alter the activity of certain connection bundles in mice and change their anxiety levels. For this work, she was awarded the Young Investigator Award in 2016. Here, in part one of her interview, she reflects on her hopes for her field of research and career, and discusses the importance of advocating for yourself.
What is most exciting to you about the future of optogenetics?
Big picture, I am most excited about how groups in the scientific community working on diverse biological questions can come together to organize our efforts and think critically about the approaches we use to understand neural circuits.
In the short-term, it will be most exciting to simultaneously manipulate specific inputs and record from identified subpopulations of neurons — a challenge we are working on now. This sounds simple, and in theory, it is something that we should easily be able to do, but there are a number of caveats that have to be considered. For example, red-shifted opsins have “blue shoulders,” meaning that the responsiveness to blue light is reduced but still present. This can be a challenge for working in vivo.
The most exciting possibility in the long-term is to introduce more “physiological” manipulations to the brain — manipulations that are precisely timed and played back into specific, functionally-defined (in addition to anatomically- or genetically-defined) populations of neurons. This would likely need to be introduced in a non-synchronous manner, in a closed-loop fashion, and account for the typical firing patterns with respect to the surrounding circuits onto more select cells. All of these areas are being worked on by many groups, including ours, but still require major advances, such as targeting neurons with very specific firing patterns. I remain hopeful, with the field moving so quickly.
How could a better understanding of neural circuitry change how we understand and treat mental health disorders in the next 5-10 years?
Mental health disorders are all represented as some type of perturbation to the function of neural circuits, so to me, this question is like asking, “How can having a road map of the United States help us drive from Boston to San Francisco?” It’s true that even if we had a complete understanding of all the neural circuits and their functions in the brain, it would not — in itself — lead to treatments.
But understanding neural circuitry and how it relates to behavior is almost synonymous with our ability to understand the underpinnings of mental health disorders. While having a road map of the United States doesn’t automatically propel you across the country, the map makes it possible to make a plan A and a plan B, and rank different routes based on pragmatic considerations. Similarly, understanding neural circuitry will make it possible for us to test treatments in a systematic, informed, and non-random manner that will potentially be orders of magnitude more effective than what we are doing now.
The brain is still something of a black box, at least at the level of treatment development. The field has stagnated in the absence of mechanistically novel targets, and I believe we have essentially saturated any gain from incremental, minor tweaks on existing treatments, which I discuss in a Neuron article.
You encourage your lab members to speak up for themselves about what they need to be successful. Why is providing this opportunity important for a healthy and productive lab environment?
Self-awareness of what you need to be happy and successful — whatever the definition of success is to you — is essential in research and life in general. It’s important to explicitly remind ourselves to think about what success means to us.
In my experience, people are the most efficient, creative, and inspired when they are taking care of all aspects of their life in a balanced way. I believe that happy people are more productive. However, it’s easy to fall into the trap of living for approval from others, which is not usually a path towards long-lasting fulfillment.
Having the ability to speak up for yourself is not an opportunity as much as a basic survival skill, and everyone should have it and practice it. I think of the saying adapted from a poem by Josh Billings, that “the squeaky wheel gets the oil.”
It’s important to openly communicate what you need at different phases of your development and training process to the people who can support you, because not everybody has the same needs.
I would advise all trainees to tell your mentors what you need to be happy and thrive. Also remember that your mentors weren’t trained to be mentors. They were trained to do experiments or other research, and then suddenly they were thrust into a leadership and management role that is completely unlike the training they had as a student or postdoc.
I always tell my students that if there is something wrong and they don’t tell me, then that’s their fault. If there is something wrong and they do tell me, then the responsibility is on me to try to improve it or at least thoughtfully explain why I can’t. I still rely on my mentees to teach me how to best mentor them and tailor the training to each of their needs. I have learned a lot from my mentees, but each individual is unique, and mentorship is not one-size-fits all.
What have you learned from advocating for yourself, and your lab?
Even though it may feel awkward or uncomfortable sometimes, advocating for yourself is part of our jobs. I am so grateful to my PhD mentor, Patricia Janak, for putting up with me during the first year of grad school when she offered a wellspring of pep-talks and belief in my potential.
I also looked to all of my mentors for more than just the minimum. I wanted to understand how they saw the world and what they thought about. They were more than just supervisors to me, they were role models and mentors that gave me something to aspire to become.
Advocating for our mentees is also an essential part of our jobs. They work hard for me, so I’ve got to work hard for them. It’s my responsibility to promote the work done in the lab to the world through talks and publications and to help launch the independent careers of my students and postdocs.
Talking about my lab’s research is one of the best ways for me to get critical feedback at an early enough stage that we can incorporate that feedback. Advocating for your research program can also accelerate the progression of science by communicating ideas early to help others avoid duplicating efforts, or incorporate the information in the next steps they take. Most of all, it will spark scientific discussion, which is one of the best things about this career.
Our jobs as scientists include more than just thinking about science. We need to convince others that our research is important and will be useful to others to get funding. Once the project is done, we need to communicate what we have found to others. In my opinion, communicating the science is equally important as doing the work, because if the work you’ve done stays in your lab notebook and nobody ever sees or hears about it (or understands it!), it’s as if the work was never done.
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