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Understanding the emotions behind memories
Thought LeaderProfessor Kay TyeWylie Vale-StuhlSalk Institute for Biological Studies In this interview, we talk to Professor Kay Tye and Hao Li about their latest research on memories and how we can begin to understand the emotions behind them. Could you please introduce yourself and tell us what inspired your career in neurobiology? My name is Kay Tye and I am a mother of two children, ages 6 and 9. When I was in high school, I was pretty sure that I would become a writer one day, and I had a great interest in English literature, which...
Understanding the emotions behind memories
In this interview, we talk to Professor Kay Tye and Hao Li about their latest research into memories and how we can begin to understand the emotions behind them.
Could you please introduce yourself and tell us what inspired your career in neurobiology?
My name is Kay Tye and I am a mother of two children, ages 6 and 9. When I was in high school, I was fairly certain that I would become a writer one day, and I had a keen interest in English literature, which was an "impractical choice" in a household with two parents who were scientists. I reflect on my immense privilege of being raised by a biologist and a string theorist, both of whom always seemed to love their work; but back then I was a rebellious teenager and wanted to major in English. One of the things I loved most about literature was how the stories unfold and how the characters develop and reveal themselves to us. The best literature, in my opinion, was characterized by the ability to capture someone else's subjective experience and commit it to memory.
I was curious how we can all be so different in our reactions and perceived experiences, but all have some aspects that are fundamentally the same. I became interested in psychology, and the search for answers to how the most indescribable experiences in biology are actually implemented became a pipe dream.
The neuroscience courses I was exposed to early on focused primarily on sensory and motor systems rather than the neural mechanisms of thoughts and feelings. The memory was certainly something that piqued my interest. I have many moments when I "knew" I would (maybe) become a neuroscientist, but one that is worth mentioning for the privilege of the experience that I could hardly appreciate as a newbie who had not yet completed her introductory psychology course: I met Henry Molaison, better known as case study patient HM - the man who had a bilateral temporal lobectomy that left him without a hippocampus and unable to form new memories.
Old memories were safe and crystal clear, but new memories (meeting a new person, remembering if you had lunch, looking in the mirror and being shocked to see an old man's face instead of the reflection of a younger man you knew decades ago after his temporal lobectomy).
Our memories, feelings, thoughts, and relationships with others are the processes that have fascinated me for as long as I can remember, and I am as curious as ever to understand them.
Image credit: Net Vector/Shutterstock.com
Every experience an individual has is associated with a feeling; this is called “valence mapping.” Can you please tell us more about how this works?
Almost all of our behaviors are motivated by two emotional valences: the pursuit of reward and the avoidance of punishment. As we experience the world around us, we are constantly bombarded by sensory stimuli, most of which are unimportant. We need to quickly filter out the most important information to make a decision.
To do this, our brain would assign either a positive or negative value to the environmental stimulus through learning, allowing us to use the stimulus as a cue to associate a positive or negative experience and predict future outcomes. We call this process valence assignment.
You have already conducted research on valence mapping in mice. How did this study help provide a foundation for your latest research?
We previously found that distinct amygdala neurons encode reward and punishment following associative learning. But how are external stimuli related to rewards or punishments?
In the current study, we specifically examined how amygdala neurons are shaped for coding reward or punishment and how these neurons can bind information about the predictive stimuli and outcome many seconds apart. We have previously compared transcriptomic expression profiles between these different projection-defined amygdala neurons and found that the neurotensin receptor gene is enriched in one population compared to the other. This led us to hypothesize that neurotensin might be a prime candidate for solving the valence assignment problem.
In your most recent research, you examined the feelings associated with memories. Can you tell us more about how you conducted your study?
To examine valence mapping, or how mice can associate emotions with memories, we trained mice to associate one auditory tone with sucrose reward and another auditory tone with shock punishment.
Once mice learned the association, they would approach the sucrose port in response to the tone predicting sucrose delivery and freeze or run in response to the tone predicting shock delivery.
What have you discovered?
We monitored changes in neurotensin concentration in the amygdala during learning using a new genetically encoded neurotensin sensor and found that neurotensin concentration in the amygdala was increased by reward and decreased by punishment.
Consequently, if we artificially manipulate neurotensin concentration in the amygdala using CRISPR or optogenetics, we can influence animals' behavior towards reward or punishment. More neurotensin in the amygdala –> reward; less neurotensin in the amygdala –> punishment
Photo credit: Andrii Vodolazhskyi/Shutterstock.com
In your study, you used CRISPR to isolate neurotransmitter function, the first time it has been used for this purpose. How important has this gene editing technology been to your research, and how are continued advances in the life sciences helping to lead to new scientific discoveries in other areas?
The CRISPR experiments are extremely important in our study because this approach allowed us to selectively isolate neurotensin signaling without affecting other neurotransmitters (such as glutamate) that are also delivered to downstream targets along with neurotensin. In this way, we can be sure that the effects of this CRISPR manipulation are specific to the contribution of neurotensin, but not to the other neurotransmitters released at the same time.
At some levels, progress in the life sciences is limited by the discovery of new tools that would allow us to study biological problems in much greater depth and precision.
How could your research also potentially help better understand mental health disorders such as anxiety and PTSD? Could this lead to new treatments?
Mood can fluctuate within a certain range from day to day. However, if the fluctuation is outside the range, it is considered a pathology. In general, too much positive processing (reward) leads to addictive behaviors such as gambling or drug addiction, while too much negative processing (punishment) leads to depression or anxiety.
We found that altering neurotensin release into the amygdala can produce either reward or punishment states. It allows us to modulate neurotensin to balance/compensate for the maladaptive/excessive positive or negative valence processing in the disease states.
Photo credit: Motortion Films/Shutterstock.com
What are the next steps for you and your research?
Lead author, Hao Li, is opening his own research laboratory at Northwestern University, where he will continue to research the roles of various neuropeptides in health and disease.
Where can readers find more information?
About Professor Kay Tye
Kay Tye graduated from MIT in 2003 with a major in brain and cognitive sciences and received her PhD from UCSF with a dissertation focused on how the amygdala experiences plasticity for reward learning. She completed her postdoctoral training with Karl Deisseroth at Stanford, and her work focused on targeting specific projections in the amygdala to bidirectionally control anxiety.
She founded her own lab at MIT in 2012, focusing on understanding the neural circuit mechanisms of emotional valence, where she received a position in 2018. In 2019, she moved her lab from MIT to the Salk Institute and became Wylie Chair Professor of the Systems Neurobiology Laboratory. In 2021, she became an investigator at the Howard Hughes Medical Institute.
About Dr. Hao Li
Hao was born and raised in Beijing, China, then moved to the United States after earning a bachelor's degree from Shandong University. He completed his Ph.D. in neuroscience from the Medical University of South Carolina and worked in the laboratory of Dr. Thomas Jhou. In 2019, Hao joined Dr. Kay Tye at the Salk Institute.
Hao is now an incoming assistant professor in the Department of Psychiatry and Behavioral Sciences and the Department of Neuroscience at Northwestern University.
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