The Past and Present of Neuroscience Research: An Interview with Dr. Lur and Dr. Palavicino-Maggio
Pascale Fung
Exploring the intersection between adolescent stress and neuronal processing at his lab in the Department of Neurobiology and Behavior at UC Irvine, Dr. Lur is an Associate Professor whose work is focused on studying the long-term and short-term effects of stressors on the brain via a multimodal model. Furthermore, he studies the changes in posterior parietal cortex excitatory transmission in male and female mice when exposed to adolescent stressors. His work is largely centered on mice models and the mammalian brain, allowing for translational applications of his findings to human behavior.
Spearheading aggression research in Drosophila fruit fly models, Dr. Palavicino-Maggio is an Assistant Professor in Psychiatry at Harvard Medical School who studies the fundamental neurological basis of social behavior, focusing on impulsive behaviors. In her lab, she discovered that a pair of pC1 alpha neurons were responsible for female aggression, and now continues her investigation of aggression by examining brain cells in both male and female Drosophila models.
PF: What is the “origin story” of your research, and what is your current work centered on?
CP: I was always interested in neuroscience and how the brain works, primarily because my sister had died by suicide. By studying the mechanisms behind self-aggression, which is a very impulsive behavior that often leads to suicide, I could understand how and why these behaviors happen. I look at the fundamentals of behavior, specifically aggression research, using the Drosophila fruit fly model system. I examine how circuits are speaking to each other, be it excitatory or inhibitory, and observe whether certain neurotransmitters are conserved across species. I look specifically at dopamine and serotonin, both of which are known to be heavy hitters involved in psychiatric disorders. Ultimately, my goal is to understand how impulsive behaviors happen, starting with how the animal senses a threat and turns that sensory input into the output–aggression.
GL: Most of my training focused on fundamental, basic training rather than translational research. When I started my own lab, I wanted to do something more related to human health and give back to the neuroscience community from which I received my education. Much of my lab looks at how stress experienced in early life, like in adolescence, affects neuronal circuits and cortical processing, and by extension, complex behaviors like decision-making and sensory processing. For example, working memory and attention, or other neural processes that involve the neural cortex.
PF: What was a turning point in your research career? If there was not any, what do you believe is the most rewarding part of the research process?
CP: In general, researchers aspire to reach the faculty level and become the group leader of their lab as they can then start looking into topics of research that are interesting—this was my turning point. Once I started to obtain NIH peer-reviewed, stringent funding through a transition grant, I felt that I was finally recognized as being able to stand on my own as a researcher in academia.
GL: I did my PhD in Cellular Biology, and did not look at neurons at all. My postdoc advisor, however, went out on a limb and hired me even though I lacked the skills necessary to do the work he wanted to complete in neuroscience. For that, I will forever be grateful as it allowed me to get into the field that I always wanted to be in but did not have the qualifications for. It was a big shift, but I switched fields and eventually became faculty, where I am trying to employ a similar attitude in my lab. Occasionally, I have people apply who are very enthusiastic but lack expertise in the necessary fields, so I try to give back for what was given to me and take a chance on those applicants who may not be entirely qualified.
PF: Do you see limitations in the research of nonhuman mammals and insects when applying your findings to the human brain and behavior? If so, how can we bridge this gap?
CP: With Drosophila, we often have to defend our model system since flies and humans are quite different. However, this is not too much of an issue since we are looking at fundamental neurotransmitters such as serotonin, dopamine, and GABA that are common between humans and Drosophila. The fruit fly model is therefore more of a guide to understanding how the human brain operates and enables behavior via sensory inputs and motor outputs. So, this foundational understanding then leads to studies of higher systems, which can then be validated in mammalian models.
GL: Obviously, with labs that work with mice, there is the issue in neuropsychiatric research of finding the correct model because mice’s experience of neuropsychiatric symptoms cannot be equated to that of humans. Humans can be stressed from work, traffic, or financial issues, all of which are issues that do not pertain to mice. To try to bridge this gap in translation, our stress paradigm aims to model the multimodality of the human experience of stress while also ensuring that the paradigm is relevant to mice models. This is an iterative process that is still ongoing and can hopefully eventually lead to a discovery that eliminates the negative effects of stress in humans.
PF: What has been your most surprising finding/discovery, and how do you see this impacting society?
CP: The most surprising finding in my lab was that of the sexual dimorphism of neurons that activate and lead to different patterns of aggression in Drosophila, with male and female patterns of aggression heightened to different extents. Looking at sex-specific patterns in psychiatric disorders is extremely helpful when creating therapeutics that are specific for the different genders. Similarly, with our work drawing attention to sexual dimorphic systems, the NIH now mandates that you have both female and male subjects so that researchers cannot create generalizations between both sexes as there truly is dimorphism that must be taken into consideration before presenting your findings.
GL: The sexual dimorphism Caroline mentioned is also manifest in mice models as male and female mice have similar initial reactions to stress, but their phenotypes diverge after some time passes. There is certainly merit in considering the sexual dimorphism of the neurons between male and female mice since there is more and more evidence that the same behavioral therapy cannot be prescribed for different genders. The fact that multiple model systems of both mouse and Drosophila models point in the same direction raises awareness of the importance of sexual dimorphism. More recently, labs, companies, and funding sources are aware that you cannot just group sample data from both females and males together. It seems that this incorporation is heading in the right direction at many, many levels.
PF: Do you believe there are shortcomings in the field of neuroscience research?
CP: Funding is a definite shortcoming in our field as we are always worried about how much funding the NIH will put into our research. When funding decreases, the level of competition is higher and people tend to forget why they are doing research in the first place. Similarly, when there is a lack of funding, people tend to leave science; it is grit and resilient people that stay. Also, with inflation, there is a lag between funding budgets and the rising costs of daily living that lowers the already minimal funding that can be offered. Lastly, there is a time constraint for researchers to gather data to apply for funding, and that makes it even more so stressful for both PIs and trainees. That stress feeds into the deterrence of students from research.
GL: Currently, the research pipeline is not looking too great as most people leave academia immediately after completing their PhD. Academia is extraordinarily competitive at the moment and is not paid very well, pushing many towards industry. You really have to love science to stay in academia, but even if you do love science, it may not be financially viable. If the funding is not there, students will know and when all they see is hardship and anxiety from current PIs, this can deter them from the field despite their love for science. There are only 24 hours in a day, and at some point, if gathering all the data to apply for a five-year grant ends up taking more than five years, things get out of hand. I think if academia wants to attract the next generation, we need to change something. We need to offer something that draws students in to pursue their love for science. Perhaps us academics can be better at marketing the wonder of discovery or the potential stability of jobs in academia, both of which are often bogged down by financial worries.
PF: What advice do you have for students interested in research?
CP: What we do is not measured, and we value skills that are not taught to you in the textbooks. Creativity, curiosity, and innovation are invaluable in research. Finding people who want to be collaborative as well is very important, especially for students since you have to work on a team before you graduate and get into the industry. Some students lose sight of that. Remembering the larger contribution you make to science as a whole allows you to get far in this industry, rather than looking for specific accolades. Those accolades will come naturally, but I think that it is fundamental to be curious and enthusiastic as a student. Allowing your passion to drive you while also being teachable is ideal, as science is collaborative.
About the Author
Pascale Fung (‘27) is a sophomore at Harvard College concentrating in Neuroscience (MBB).
Spearheading aggression research in Drosophila fruit fly models, Dr. Palavicino-Maggio is an Assistant Professor in Psychiatry at Harvard Medical School who studies the fundamental neurological basis of social behavior, focusing on impulsive behaviors. In her lab, she discovered that a pair of pC1 alpha neurons were responsible for female aggression, and now continues her investigation of aggression by examining brain cells in both male and female Drosophila models.
PF: What is the “origin story” of your research, and what is your current work centered on?
CP: I was always interested in neuroscience and how the brain works, primarily because my sister had died by suicide. By studying the mechanisms behind self-aggression, which is a very impulsive behavior that often leads to suicide, I could understand how and why these behaviors happen. I look at the fundamentals of behavior, specifically aggression research, using the Drosophila fruit fly model system. I examine how circuits are speaking to each other, be it excitatory or inhibitory, and observe whether certain neurotransmitters are conserved across species. I look specifically at dopamine and serotonin, both of which are known to be heavy hitters involved in psychiatric disorders. Ultimately, my goal is to understand how impulsive behaviors happen, starting with how the animal senses a threat and turns that sensory input into the output–aggression.
GL: Most of my training focused on fundamental, basic training rather than translational research. When I started my own lab, I wanted to do something more related to human health and give back to the neuroscience community from which I received my education. Much of my lab looks at how stress experienced in early life, like in adolescence, affects neuronal circuits and cortical processing, and by extension, complex behaviors like decision-making and sensory processing. For example, working memory and attention, or other neural processes that involve the neural cortex.
PF: What was a turning point in your research career? If there was not any, what do you believe is the most rewarding part of the research process?
CP: In general, researchers aspire to reach the faculty level and become the group leader of their lab as they can then start looking into topics of research that are interesting—this was my turning point. Once I started to obtain NIH peer-reviewed, stringent funding through a transition grant, I felt that I was finally recognized as being able to stand on my own as a researcher in academia.
GL: I did my PhD in Cellular Biology, and did not look at neurons at all. My postdoc advisor, however, went out on a limb and hired me even though I lacked the skills necessary to do the work he wanted to complete in neuroscience. For that, I will forever be grateful as it allowed me to get into the field that I always wanted to be in but did not have the qualifications for. It was a big shift, but I switched fields and eventually became faculty, where I am trying to employ a similar attitude in my lab. Occasionally, I have people apply who are very enthusiastic but lack expertise in the necessary fields, so I try to give back for what was given to me and take a chance on those applicants who may not be entirely qualified.
PF: Do you see limitations in the research of nonhuman mammals and insects when applying your findings to the human brain and behavior? If so, how can we bridge this gap?
CP: With Drosophila, we often have to defend our model system since flies and humans are quite different. However, this is not too much of an issue since we are looking at fundamental neurotransmitters such as serotonin, dopamine, and GABA that are common between humans and Drosophila. The fruit fly model is therefore more of a guide to understanding how the human brain operates and enables behavior via sensory inputs and motor outputs. So, this foundational understanding then leads to studies of higher systems, which can then be validated in mammalian models.
GL: Obviously, with labs that work with mice, there is the issue in neuropsychiatric research of finding the correct model because mice’s experience of neuropsychiatric symptoms cannot be equated to that of humans. Humans can be stressed from work, traffic, or financial issues, all of which are issues that do not pertain to mice. To try to bridge this gap in translation, our stress paradigm aims to model the multimodality of the human experience of stress while also ensuring that the paradigm is relevant to mice models. This is an iterative process that is still ongoing and can hopefully eventually lead to a discovery that eliminates the negative effects of stress in humans.
PF: What has been your most surprising finding/discovery, and how do you see this impacting society?
CP: The most surprising finding in my lab was that of the sexual dimorphism of neurons that activate and lead to different patterns of aggression in Drosophila, with male and female patterns of aggression heightened to different extents. Looking at sex-specific patterns in psychiatric disorders is extremely helpful when creating therapeutics that are specific for the different genders. Similarly, with our work drawing attention to sexual dimorphic systems, the NIH now mandates that you have both female and male subjects so that researchers cannot create generalizations between both sexes as there truly is dimorphism that must be taken into consideration before presenting your findings.
GL: The sexual dimorphism Caroline mentioned is also manifest in mice models as male and female mice have similar initial reactions to stress, but their phenotypes diverge after some time passes. There is certainly merit in considering the sexual dimorphism of the neurons between male and female mice since there is more and more evidence that the same behavioral therapy cannot be prescribed for different genders. The fact that multiple model systems of both mouse and Drosophila models point in the same direction raises awareness of the importance of sexual dimorphism. More recently, labs, companies, and funding sources are aware that you cannot just group sample data from both females and males together. It seems that this incorporation is heading in the right direction at many, many levels.
PF: Do you believe there are shortcomings in the field of neuroscience research?
CP: Funding is a definite shortcoming in our field as we are always worried about how much funding the NIH will put into our research. When funding decreases, the level of competition is higher and people tend to forget why they are doing research in the first place. Similarly, when there is a lack of funding, people tend to leave science; it is grit and resilient people that stay. Also, with inflation, there is a lag between funding budgets and the rising costs of daily living that lowers the already minimal funding that can be offered. Lastly, there is a time constraint for researchers to gather data to apply for funding, and that makes it even more so stressful for both PIs and trainees. That stress feeds into the deterrence of students from research.
GL: Currently, the research pipeline is not looking too great as most people leave academia immediately after completing their PhD. Academia is extraordinarily competitive at the moment and is not paid very well, pushing many towards industry. You really have to love science to stay in academia, but even if you do love science, it may not be financially viable. If the funding is not there, students will know and when all they see is hardship and anxiety from current PIs, this can deter them from the field despite their love for science. There are only 24 hours in a day, and at some point, if gathering all the data to apply for a five-year grant ends up taking more than five years, things get out of hand. I think if academia wants to attract the next generation, we need to change something. We need to offer something that draws students in to pursue their love for science. Perhaps us academics can be better at marketing the wonder of discovery or the potential stability of jobs in academia, both of which are often bogged down by financial worries.
PF: What advice do you have for students interested in research?
CP: What we do is not measured, and we value skills that are not taught to you in the textbooks. Creativity, curiosity, and innovation are invaluable in research. Finding people who want to be collaborative as well is very important, especially for students since you have to work on a team before you graduate and get into the industry. Some students lose sight of that. Remembering the larger contribution you make to science as a whole allows you to get far in this industry, rather than looking for specific accolades. Those accolades will come naturally, but I think that it is fundamental to be curious and enthusiastic as a student. Allowing your passion to drive you while also being teachable is ideal, as science is collaborative.
About the Author
Pascale Fung (‘27) is a sophomore at Harvard College concentrating in Neuroscience (MBB).