Abstract: Learning and memory are essential topics in neuroscience as they are associated with several diseases and conditions. However, we are yet to understand how learning and memory works on the molecular level. Synaptic plasticity is widely accepted as the cellular correlate of learning and memory. Trafficking of AMPA receptors (AMPARs) into and out of the synapses is critical to many forms of synaptic plasticity including long-term potentiation (LTP) and long-term depression (LTD). Many proteins regulate the trafficking of AMPA receptors, including KIBRA. Previous research shows that KIBRA knockout mice have deficits in synaptic plasticity, as well as learning and memory. Although this evidence suggests that KIBRA alters the trafficking, direct molecular evidence is still lacking. Alteration in AMPAR number, location, and post-transcriptional modifications all effect the availability for AMPARs to be trafficked into and out of the synapse. Previous data suggests that KIBRA regulates the amount and trafficking of proteins, but how it influences AMPAR and AMPAR complexes in vivo remains unknown. Here, we wanted to identify specifically whether KIBRA influences proteostasis or the trafficking of AMPA receptors through phosphorylation. We used sub-cellular fractions from tissue of CA1 hippocampal neurons from WT and KIBRA KO mice. From these data, we preliminarily identified that a loss of KIBRA changes the steady-state expression of AMPARs in discreet cellular fractions. Additionally, we also discovered that a loss of KIBRA significantly increases the baseline phosphorylation of AMPARs. Collectively, these results indicate that KIBRA might influence the number of AMAPRs, the trafficking of AMPARs, and the post-translational modification of AMPARs. Email:[email protected]
What Does Research Mean To You? As a very curious person, I believe research can be the answer to the countless questions we may have regardless of the field or subject. It gives us the opportunity to find new information that has never been known before. Through research, one can also learn to be very creative as there is no definite or established way to find something new. In medicine, research is especially important to be accurate and efficient in treating not just the patient, but the 'disease' as a whole. I believe that the fundamentals to medicine and treatments lie in research and it has been playing a major role through decades of medical advancements.
Tell Us About Your Journey I had minimal experience before I participated in the Volk Lab through the Green Fellowship Program. Hence, I wasn't familiar with most of the techniques or the lab procedures. I was also late in being prepared to work on my own individual project because I was relatively new. However, my lab mentors helped me a lot throughout the semester so that I could learn from what I was doing and enjoy the experiments. After a lot of reading and practice, I was finally able to get on my project. One thing I learned throughout this experience was to keep trying. Although it's really fun to be in the lab and try to discover something new, it does require immense effort and patience. It's natural that the experiments don't always go as planned and that we fail countless times in the lab. It is really important to have the dedication to accept failures gracefully and learn from what went wrong. And when the experiment does go well, it's a beautiful feeling. Reading research articles, experimenting, and discovering information about the proteins in the brain has strongly motivated me to be involved in research throughout my life. Thus, this fellowship is an incredible opportunity to really know what it feels like to be working in a lab like graduate students and I would highly recommend it to anyone who is interested.
How Did the Pandemic Affect Me? As the COVID-19 cases spiked and we were asked to stay at home, all of our research activities took place on a computer. Although I initially thought my fellowship is essentially over, I was able to make immense progress staying at home. It made me realize that lab is not the only place where we can actively participate in research. Of course, you would need equipments to do the actual experiments but what I realized is that a major portion of research is analyzing what we have already found out. Figuring out what the discovery means or how it affects the already existed information is crucial. Overall, I would say that even with the pandemic, it was a new and unique experience.
Advice for Future Green Fellows
You probably have heard this before but I want to stress on how you shouldn't be afraid to ask questions!! As a person who has been in the program and had no idea what was going on for weeks, I want to assure you that it's fine to be lost towards the beginning. In fact, after the interview, I was sure that I wasn't going to be selected because I felt I didn't know enough to be in this program. Remember that everyone is here to learn and the program is meant for you to learn and see what it is like to be in a lab! Although it can feel really intimidating in the lab with all the graduate students and your PI, remember that they are always open to answer questions and teach you. You will figure everything out with time! Also, feel free to contact with any questions you may have :)