Hughes Mentor:  Christiane Linster

Department: Neurobiology and Behavior

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Life in the Rat Lab

The first thing people usually ask me when I tell them I work with rats is whether or not I get bitten – and, if yes, whether or not I have rabies (as a joke, or at least I think). However, the possible hazards of working in Christiane Linster’s laboratory in Mudd Hall are minimal. For me, the true challenge of working in the lab this summer was to be as flexible, critically observant, and patient as possible, under the circumstances, which I will discuss further along this essay.

Although some people may have a natural aversion toward the rodent population, rats can actually be pretty adorable—that is, once you can get past the rather long, hairy, worm-like tail that can substitute as a whip when its agitated owner is being held up in mid-air by a determined undergraduate. Despite the feisty attitude of my fellow specimen, however, Sprague-Dawley rats have been commonly used in many labs for their acute olfactory sense and intelligence in quickly learning and performing trained tasks. Thus, the twelve rats appointed to me this summer were handled, fed, and trained with high hopes. Each was given a specific number, a partner in a bedding-filled cage, and shaped, or trained, to dig in ceramic pots filled with odor-scented bedding for a reward, which was a broken piece of a Fruit Loop that had been baked beforehand to reduce its sweet odor.

To be specific, my research centered around the short-term olfactory memory of Sprague-Dawley rats and the effects of an acetylcholine antagonist on the rat’s working memory of the odor stimulus. My initial plan was to first train the rats to perform a task that would require the use of short-term memory, dubbed a “Match-To-Sample Task” in previous studies involving animal-behavior tests. Pairs of odor stimuli that have both chemically different and similar structures were to be used in the task to see which task the rats would find more difficult to perform based on their working memory. The hypothesis was that using odors with chemically similar structures would make it more difficult for the rat to perform the task. Since olfactory receptors are broadly tuned to bind to a variety of different odor molecules with areas of similar structures rather than just one odor molecule, the rat should have more difficulty remembering which odor it just sniffed when presented with the task of choosing between two odor stimuli whose odorants have chemically similar structures. After the rats would be trained to perform the task with a significant amount of accuracy, I planned to perform a cannulation surgery, which involves the insertion of two thin, sterile tubes through the skull directly into the olfactory bulb of the rat to facilitate the direct injection of my drug of choice, namely an acetylcholine receptor antagonist called scopolamine. Scopolamine has been used in previous studies involving short-term memory tests on rats to show that blocking acetylcholine from binding to its receptors by administration of this antagonist would impair one’s ability to store the memory of a recently presented stimulus.

After the protocol was finalized, I came into the lab every morning to set up my pre-determined odor pairs, which were presented in the form of pots filled with odor-scented bedding. The rat was placed in a plastic cage with two chambers, starting and testing chambers; a sample odor pot was placed in the starting chamber for the rat to sniff, and then after a designated delay period, the rat was released to the testing chamber to choose between two odor pots, one of which had the same odor as the sample odor and thus contained a reward.

Unfortunately, most of my rats were unable to perform the match-to-sample task in the way I had hoped, due to their reliance on the odor of the baked Fruit Loop rather than their short-term memory of the sample odor stimulus to pick the correct pot. I switched the reward to sugar pellets, which were supposedly odorless. Because the rats’ sense of smell was acute enough to distinguish the smell of the sucrose pellets from the odor-scented bedding, I resorted to crushing fruit loop powder and mixing that into the bedding before returning to the use of Fruit Loops as the reward. Because I had to train the rats to learn the rule of remembering the sample odor to guide them in choosing the right odor in the testing chamber, this entire process took almost two month’s worth of training.

The valuable lesson I learned this summer through the Hughes program was that research takes an immense amount of patience as well as a critical eye to take note of anything that might be going wrong. For the sake of accurate results, it was incredibly important to be perceptive and observant of the means or manner by which research results are attained. Even though much of my experimental plans did not proceed as I had initially hoped, I did realize that research itself is a science; one must experiment and determine which method is the most effective for attaining the best results as possible. Time is a necessary sacrifice in the quest for meaningful results.

In conclusion, I would like to recommend that students considering being a part of undergraduate research be willing to dedicate their time to finding a good laboratory that fits one’s interests. I feel fortunate and honored to be a part of the neurobiology lab where I am currently working, and I believe that students should really take advantage of the research opportunities offered at Cornell, for it is well worth the time. I would also like to emphasize that students be open to the idea that good results are not always so easy to gain and that research does take time; however, the skills gained in a research laboratory through hands-on experience are those that can be learned nowhere else.

My Undergraduate Research Experience

The life of an undergraduate is hectic, especially if you are an undergraduate at Cornell. As a freshman, I can remember being overwhelmed with all the unexpected challenges and issues flying at me from various directions—the unruly suitemates, the hours of homework and reading assignments, the questionable dining hall food, the terrifying prelims. With all of that on one’s plate, who has time to consider research? I certainly believed there was no way I could juggle research with academics. However, that was until I took Bio NB221: Introduction to Behavior.

I was enthralled by the range of topics covered in the course, all of which were related to animal behavior. Listening to professors divulge the secrets of the honeybee dance, explain the process of forming and recalling memories, and discuss underground societies of naked mole rats made me want to get involved in research as well. I was inspired by how much we have already learned about the world and ourselves from our animal friends.

My first lab experience was at New York University the summer after my sophomore year. I contacted NYU’s Professor Joseph LeDoux after learning about his work in Bio NB221 and ended up assisting one of his post-doctorates in a project on post-traumatic stress disorder. Using rats and auditory fear conditioning experiments, we investigated the effects of the drug propranolol on memory reconsolidation—the process by which vulnerable, recalled memories are re-crystallized / re-stored and saved from being forever forgotten. It was found that propranolol can actually block the process of reconsolidation and hence effectively erase one’s memory. I was thrilled and excited at the notion that my work could one day save people from lives fraught with depression and fear.

As the summer came to a close, I found myself wishing my research experience would not end. Thus, I began searching for research opportunities at Cornell. After emailing a number of professors (all of whom were involved in neurobiology), I landed a spot in Professor Christiane Linster’s computational physiology lab. The fit was perfect, because my NYU experience equipped me with knowledge of the same techniques used by those in Professor Linster’s lab. Most importantly, I had already learned how to perform rat cannulation surgeries, a process used in many of Professor Linster’s experiments.

As mentioned previously, I was initially worried that I would not be able to balance academics and research. The perfect solution was to enroll in BioG 499, a course that offers students credit for the hours they spend in their research labs. As a result, I was able to substitute research for an elective course and eliminate any concerns I had about time management problems.

I have been working on my own project for three months now. It is a survey of the effects of the neurotransmitter dopamine on olfactory discrimination. Before beginning my research, I had to have a thorough understanding of basic neurochemistry, including the mechanisms by which action potentials and neurotransmitters function to transmit information about the outside world to the brain. Such background knowledge helps me explain and discuss the results I have been accruing over this summer.

My project involves rats as subjects. Because they are kept on a 12 hour light/dark cycle that begins at 6am everyday, they are most aware and active in the early morning hours. My typical day in the lab begins before the sun has completely risen. The rats are given odor discrimination tasks after dopamine receptor regulators are injected directly into their olfactory bulbs. After four to five hours of behavioral testing, I spend the afternoon compiling and analyzing the day’s data. Because my project is time intensive, I hope to have all my data collected by the time the academic year begins.

Having done research for nearly an entire year now, I have learned a great deal. For instance, I now realize that the experimental process is by no means set in stone. One’s project is constantly evolving as new questions arise, techniques are perfected, and mistakes are realized. I am now on my third round of behavioral testing. I initially redid my experiment because we realized the rats are more responsive in the early morning. I am now re-doing my experiment in order to control for a variable we had not even considered previously. Research is similar to the writing process. No matter how many times you re-read an essay, you will always find things to change and improve. Likewise, no matter how many times you conduct an experiment, you will always be able to devise alternatives and addendums to your procedure. I also now realize that the scientific arena is like one giant web of ideas. Individuals in the scientific community feed off of one another’s projects. One person’s results can lead to another’s hypothesis. Thus, scientific inquiry will never reach a plateau.

My laboratory experiences have also taught me about myself. I was initially intimidated by heading my own project, but I am proud to say that I rose to the occasion. I am now more confident in my ability to take on intellectual challenges. I also now realize that I learn much more by having “hands-on” experiences. The concepts discussed in my neurobiology courses only truly meant something to me when I began doing research, for I could finally see them “in action.” Additionally, doing research has taught me how to handle minor setbacks and failures without getting overly stressed out and how to more efficiently manage my time.

This upcoming fall I will be a student advisor to incoming biology majors. I will definitely recommend each of them get involved in research at some point in their four years as undergraduates. It is a useful and stimulating way to spend one’s time. I know that when I look back at my college career years from now, I will be very happy I was an undergraduate researcher.

Writing Assignment – A Hughes Scholars Guide to doing Research in the Linster Lab

The Linster Lab, in the Department of Neurobiology and Behavior, uses the olfactory system as a model for studying neural coding, neural modulation, and aspects of memory processes. Researchers work with rats, mice, frogs, and honeybees using behavioral, electrophysiological, and computational modeling tools.

To appreciate the work that occurs in this lab, a background in neurobiology and behavior is important. I recommend taking courses like BioNB 221 and 222 before trying to work in Linster Lab. Undergrads typically start out assisting on other projects and then work on a project of their own after a semester or two.

Depending on the project I am working on, a typical day for me could include slicing brains onto slides, conducting behavioral tasks with rats or mice, or performing neuro-surgeries on rats. During the summer, I arrive around 9 AM, check email, and then go about whatever task I have planned to do. Lunch is usually around noon, and behavior tasks usually take up the afternoon.

Some important techniques I do are perfusions on animals – which are procedures that sacrifice the animal and allow us to preserve its brain for further examination. I also could use the cryostat, which is something similar to a deli-slicer used to make slides of tissue samples.

Doing this project, I have learned that research can be very tedious from day to day. It is important to be able to step back and appreciate the ultimate goal of the work you are doing in order to deal with the tedium. I have learned that I was not aware of the tedium of research until I had this summer experience.

The major difference between summer research and research during the school year is time. In the summer, much more can be accomplished since you are in the lab 8 hours a day. In the school year, courses tend to prevent the same amount of progress.

Dr. Christiane Linster

Dr. Christiane Linster is an associative professor in the Department of Neurobiology and Behavior. She also runs the Computational Neurophysiology Lab at Cornell. At the moment Dr. Linster is focusing on learning and memory in the olfactory system using a synthesis of behavioral experiments, electrophysiological studies, and computer modeling.

Dr. Linster was born in Luxemburg, a very small country tucked between Belgium, Germany, and France. Dr. Linster was not the type of person who knew they wanted to study biology from an early age. As a child she studied classical clarinet and conducting at the Academy of Music in Graz, Austria. This is when she first became interested in the science behind the music she was creating. She decided she wanted to be become a sound engineer, and the path to this was through electrical engineering. She graduated from Technical University with a masters in electrical engineering in 1989. Her thesis was titled Get Rhythm: A Musical Application for Neural Networks. It is here that you can see the first inklings of Dr. Linster’s interest in neurobiology.

Dr. Linster then moved to Paris in 1990 to partake in graduate studies at Pierre and Marie Curie University. Here she earned a PhD in applied physics. But you can still see hints of her future work and fondness for neurobiology in her thesis, titled Formal Neural Networks and Olfaction: Modeling Pheromone Processing in Insects, Suma. It was her PhD advisor here that first got Dr. Linster really interested in neurobiology while working on olfaction and classical conditioning in honey bees. Dr. Linster became firmly rooted in neuroscience when she did post-doctorial work on in vivo electrophysiology and theoretical modeling of olfactory processing and memory at Harvard University. Soon after, she became an associative professor of neurobiology and behavior here at Cornell University.

You can see that Dr. Linster did not take the classical route to a career in neurobiology. It was through the influence of here advisors and colleagues when she was in undergraduate and graduate school that help shape her path. This is one of the reason Dr. Linster likes working with undergraduates who want to learn research. She hopes she can help them as much as her mentors had helped. Dr. Linster has a fondness for teaching (she also teaches several courses, including introduction to neuroscience) and believes work experience can help you learn certain things better than any lecture.

Dr. Linster’s unique training background also affects her work today. She is the head of the Organization for Computational Neuroscience. Computational neuroscience is basically the study of how the brain computes. What is unique about computational neuroscience is its approach to this question. Dr. Linster uses a combination of brain imaging, electrophysiological recordings, computer simulation of brain structures, and behavioral experiments. Needless to say, her background in physics and engineering play a big role in why she chose this approach. Dr. Linster believes computational neuroscience allows you study a system, like olfaction, in many different ways and allows you to create theories that connect different levels of analysis, like observable behavior to an area of the brain to activity of a few neurons.

Currently, Dr. Linster is working on the role of neuromodulators in memory. Neuromodulators are a type a neurotransmitter. Neurotransmitters are chemical signals involved in neuron to neuron communication. Neuromodulators are a type of transmitter that is not directly involved in neuronal communication, but rather shapes the characteristics of the conversation. Neuromodulators are like a dimmer switch on a light; they cannot turn the light from off to on, but if something turns the light on (i.e. a classical neurotransmitter), modulators can alter the amount of light. Dr. Linster focuses on the role of these modulators in the olfactory bulb (were smell sensory input is relayed from the nose) of mice. Different behavioral experiments are performed involving mice being able to remember and associate certain smells. Then these experiments are performed on mice which have been injected with certain neuromodulators and the results compared. Electrophysiological recordings from the olfactory bulb in the presence of different smells and different modulators are also done. From all this information, computer models of the olfactory bulb and how its activity changes in response to different smells and modulators can then be made and used for further studies. Dr. Linster hopes her research may help discover the underlying causes of memory loss and diseases like Alzheimer’s. She believes it is the breakdown of specific modulators that causes memory loss. The next step in Dr. Linster’s research may involve some molecular techniques, involving behavioral experiments with mice genetically predisposed to Alzheimer’s.

Dr. Linster is doing some very interesting work and her approach to research science is distinct and comprehensive, borrowing from many different fields and synthesizing them into one sound theory. She loves to teach and encourages undergraduates to seek out experience in research. She has participated in the Hughes Program for several years and is eager to have undergraduates in her lab. Her lab is located in W249 Mudd Hall. Email: cl243@cornell.edu.