Pooja Gupta ’16 is one of three Brandeis undergraduate students working alongside Professor John Lisman ’66 on a project seeking to discover how to erase a memory and to delineate the chemical processes involved in the retention of long-term memory. In an exclusive interview with The Brandeis Hoot, Gupta discussed the project, her experiences in the lab, as well as her personal aspirations in the medical and scientific worlds.
In the spring of her first year, Gupta applied to several labs, eager to begin research. She secured an interview with Lisman, though at the time, he did not have a position available. Gupta, however, stayed in contact with Lisman and when she touched base with him in the fall of her sophomore year, he had a project in mind.
Memory is caused by long-term potentiation (LTP), the process by which the hippocampus, a major component of our brains, converts short-term memory to long-term memory. The university’s study seeks to confirm the brain chemicals involved in this process and to better comprehend how a breakdown of this construct will affect memory.
Current research suggests that the enzyme, Calcium/Calmodulin-dependent protein kinase II (CaMKII), plays a significant role in memory. CaMKII interacts with an ion channel called the NMDA Receptor. This reaction strengthens LTP, which thereby strengthens memory. Research has shown, however, that when this process does not run smoothly, memory is sabotaged.
The research team at Brandeis is working with the Herpes Simplex Virus (HSV) to study how it may impact this construct. HSV is a transient virus that interacts with the CaMKII, making it unable to bind with the NMDA and, furthermore, unable to strengthen LTP. After 10 days, the virus goes away and, hopefully, does not affect any other aspects of the brain.
Gupta explained the main goal of her study.
“We want to justify that CaMKII is the memory protein by proving that we can erase a memory,” said Gupta. “Our way to prove this is by doing behavioral testing with adult male rats.”
The team plans to inject the rats with HSV and observe how it impacts their long-term memory. They will inject various other viruses as controls and extremes in order to be sure that CaMKII is the true memory protein. There is, however, an important first step before the aforementioned observations can take place.
“Before we can erase a memory, we have to instill a memory,” Gupta explained.
In the lab, the team places rats on a rotating platform with a shock zone and series of markings on the wall. As the platform spins, the rats must figure out where they are, based on their memory of the wall patterns, in order to avoid the shock zone. After the virus is inserted, the rats should forget the patterns and are shocked. This would prove that the inability of the CaMKII to interact with the NMDARs is the root of memory loss.
Currently, the project is in the early stages. Gupta and the others are working to train the memories of the rats. They are also practicing the injection of chemicals into the rat brain using a green fluorescent protein (GFP) in place of the real virus. The GFP indicator allows them to see whether or not they are injecting into the right area of the brain.
The project is, however, in need of funding in order to advance further. Lisman is currently writing a grant proposal, incorporating results provided by Gupta and the other students, which, if approved will allow the project to take a major leap forward and begin the testing of the actual viruses. Gupta spoke about the stress of constantly trying to convey why the study is important and where it could lead in order to make these requests for funding, knowing that arguments will not always be well received and requests will not always be accepted.
Gupta is double majoring in neuroscience and biology. She has always been interested in science, but a turning point came when she took A.P. Psychology in high school. The class piqued her interest in the inner workings of the human brain, and she became fascinated in the reasons behind its behaviors on a chemical level. And after taking her first neuroscience class at Brandeis, she knew she wanted it to be her major.
Gupta chose to study biology to provide her with a solid foundation of all the sciences and to prepare her for research. Over time, however, Gupta has come to find that she is more interested in pursuing a career in a medicine than in research. She plans to go to medical school after graduation and begin working in a hospital.
“I think I might want to be a neurologist or a psychologist, so I can work with people with brain traumas,” she said.
Despite the realization that her future does not lie in the lab, Gupta has enjoyed her time spent on the project.
“The lab is a really good environment to be in,” said Gupta, explaining that although at first she felt shy around her partners in the lab, they now they get along and mesh very well together.
For Gupta, the most rewarding part of the work has been attaining results, specifically favorable ones. A huge smile flashes across her face as she describes the joy of finding a rat that could successfully avoid the shock zone on the platform. “We got one rat that was just so good and he remembered [the patterns] perfectly,” she said.
The research team is now using this training method for other rats moving forward. Gupta mentioned that the majority of the rats are performing better now than at the beginning of the summer.
“Right now, it’s a lot of trial and error,” said Gupta. “I’ve come to understand that research is a very long process that requires a lot of patience.”
If successful, the project has the potential to incur strong advances in health science. Studies have shown that decreased LTP can lead to diseases such as Alzheimer’s, epilepsy, addiction, Angelman Syndrome and cell death during stroke. As the project builds a new understanding of the components and reactions involved in memory making, the world seeks to gain a wealth of information applicable to these diseases. If students are able to learn how and why they come about, we are one step closer to finding cures.
