cornell
synapse THE UNDERGRADUATE JOURNAL OF NEUROSCIENCE
cornell
synapse
THE UNDERGRADUATE JOURNAL OF NEUROSCIENCE VOLUME 9 2015 EDITORS-IN-CHIEF Jimmy Guo ‘16 Devon McMahon ‘15
MANAGING EDITOR Nikil Prasad ‘17
CONTENT EDITORS
WRITERS
Drew Adler Joseph An Erika Glaubitz Jeanie Gribben Justin Hall Aleena Jafri Jacob Kolenda Brian LaGrant Max Levinson Julie Mina Derek Nie Stephanie Yan
Mary Abramczuk Joseph An Shivansh Chawla Zach Griffin Jacob Kolenda Brian LaGrant Nicole Levine Kamal Maher Derek Nie Sarah Park Erica Sadler Sanjna Surya Jane Wei Faculty Advisor: Dr. Carl Hopkins
© 2015 Cornell Synapse
Vol 9 | 2015
TABLE OF CONTENTS NEWS 3 4
The Importance of Curiosity in Learning
5
The Fabric of Time and Space in the Hippocampus
6
Caffeine: Alertness, Long-Term Memory, or Both
8
How Cannabis Consumption Affects the Brain
9
What Your Hometown Says about Your Future Health
BDNF and its Function in Crack Cocaine Addiction
FEATURES 11
Eliza Baird-Daniel
13
Katarina Cheng
15
Wei-Feng “Aaron” Lee
17
Nicholas Petersen
19
Roshansa Singh
21
Nathan Sklar
© 2015 Cornell Synapse
Vol 9 | 2015
NEWS
The Importance of Curiosity in Learning Derek Nie
Writer & Editor Have you ever tried pulling an all-nighter but the information just didn’t seem to stick? While other times you barely studied, but everything clicked for the exam? How to learn better is a question applicable not only to students, but also to those looking to get an edge in a competitive job market, seeking to hone their skills in a current position, or simply wanting to pick up a hobby. In a 2014 study by Gruber et al., scientists at the University of California at Davis attempted to shed light on the relationship between curiosity and learning. Specifically, they looked for a correlation between curiosity and memory retention. They found that states of high curiosity led to activation in three main areas of the brain that led to better memory retention of not only the information that subjects were trying to learn, but also incidental information that was encoded during the learning process. The experiment consisted of two phases: the screening phase and the study phase. In the former, subjects chose a rating for how likely it was that they already knew the answers to a set of trivia questions presented to them, and to what degree they were curious to know the answers. Only questions that the subjects rated as being highly curious toward or not very curious toward were used during the next phase of the experiment. The study phase took place inside an fMRI scanner. A trivia question was presented from the pool selected in the screening phase. Once the question was presented, a 14-second long period of anticipation began in which participants were also exposed to incidental information. In this study, the incidental information Š 2015 Cornell Synapse
was a face unrelated to the trivia question. During this anticipation period, the researchers observed brain activity to locate regions associated with curiosity. After this phase, participants were presented the answer and given time to study it. For each trial, after a time delay of twenty-four hours, each participant was re-tested in the scanner for retention of the answers to the trivia questions given in the first study phase. The results of the experiment led to the conclusion that states of high curiosity led to greater activation in three areas of the brain: the SN/VTA areas of the midbrain, the hippocampus, and the nucleus accumbens. In previous studies, activity in the SN/VTA were important for motivation, reward sensing and addiction. The hippocampus is known to play an important role in memory formation for both short-term and longterm memories. Recent studies have also shown that hippocampal activity can affect memory formation during the anticipation of a reward [Shohamy and Adcoc, 2010]. Finally, the nucleus accumbens is known to have important effects on motivation, reward, and pleasure. During the anticipation phase for questions that elicited states of high curiosity, more activity was observed in the SN/VTA and nucleus accumbens compared to questions that elicited low states of curiosity; however, no significant difference was observed in the hippocampus. During presentation of the answers, no significant effects were observed. In the second study phase, participants were found to recall significantly more answers to questions that elicited high curiosity as compared to questions that elicited low curiosity. Activity in the nucleus accumbens during anticipation of trivia answers predicted memory formation for questions associated with high-curiosity but not low curiosity. In contrast, for the SN/VTA, activity predicted memory recall but there was no specificity based on curiosity. Activity paralleling that of the nucleus accumbens was found for regions of the right hippocampus, but not for the 3
Vol 9 | 2015
NEWS
left hippocampus, explaining the lack of significant activity overall as found in the anticipatory phase. Curiosity was also found to correlate with better retention of incidental information, in terms of more faces remembered for those presented during anticipation of questions that elicited high curiosity, rather than those of low curiosity. The neural connections between SN/VTA and the hippocampus, which rely on the neurotransmitter dopamine, also showed increased activity during states of higher curiosity. In summary, surprising differences were found in activity in the areas of the SN/VTA and the nucleus accumbens in terms of memory retention of the trivia answers as opposed to incidental information. Major activity was observed only during the anticipatory phase of learning new information, not in following events where information was recalled. These results are important in that they suggest areas
of potential for future research in the effect of curiosity on learning. These findings could also have implications in terms of the neurological basis of memory loss and inhibited memory formation in elderly patients, along with psychiatric disorders that affect dopamine transmission. In addition, for those trying to optimize their learning, helpful strategies may consist of promoting interest in a subject and assessing motivation in learning it.
BDNF and its Function in Crack Cocaine Addiction Jacob Kolenda
from the drug after repeated doses. Its presence in the VTA also elicits the formation of drug-conditioned cues and an increase in drug-seeking behavior. BDNF infusion into the prefrontal cortex, however, suppresses cocaine seeking behavior (Whitfield, et al. 2011). A recent study (Hillburn et al., 2011) has implicated BDNF as a biomarker, a molecule which indicates the abnormality of a certain condition, for the severity of
Drug addiction consists of compulsive drug-seeking behavior regardless of negative social and occupational consequences, accompanied by relapse and withdrawal during periods of abstinence. Even though understanding the neurobiological pathways that establish these characteristics is a difficult process, researchers are constantly uncovering new mechanisms surrounding drug addiction. Brain-derived neurotrophic factor (BDNF) is the most abundant neurotrophin (a type of that helps neurons survive) in the brain and acts as a growth factor that promotes the development, survival, and function of neurons. This protein also plays an essential role in cocaine addiction. When infused into the ventral tegmental area (VTA), a region of the brain heavily involved in drug interactions, BDNF causes sensitization to cocaine, which leads to an increased effect
relapse, drug craving, and withdrawal. While a previous paper (D’Sa et al., 2011), showed a positive correlation between BDNF levels and relapse rates, another study (Corominas-Roso et al., 2012) has found that individuals who remain drug abstinent exhibit higher BDNF
Writer & Editor
Š 2015 Cornell Synapse
References: Akers, K. (2014). Hippocampal Neurogenesis Regulates Forget ting During Adulthood and Infancy. Science, 344(6184), 598602. Retrieved October 16, 2014. Jiang, W. (2005, 12). Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects. Journal of Clinical Investigation, 115(11), 3104-3116. doi: 10.1172/JCI25509 Scharfman, H. E., & Hen, R. (2007, 12). NEUROSCIENCE: Is More Neurogenesis Always Better? Science, 315(5810), 336-338. doi: 10.1126/science.1138711
4
Vol 9 | 2015
NEWS
levels. Therefore, the role of BDNF expression in the early stages of withdrawal remains relatively uncertain. Von Diemen’s recent paper attempts to provide some new insight into this topic by evaluating BDNF levels before and after the withdrawal period of crack cocaine usage and examining the correlation between the presence of BDNF and patterns of drug use. He studied a group of 78 males over 18 years old who had been hospitalized for crack cocaine usage. Blood samples were taken once within 24 hours of a subject’s admission into the hospital and again 24 hours before discharge. The BDNF levels found in these samples were then compared to those from a control group of healthy individuals. BDNF levels in the treatment subjects were found to be much lower at admission when compared to the control group’s levels. At discharge, they exhibited BDNF levels similar to those of the controls. This indicates that BDNF increases during early crack cocaine withdrawal. However, this escalation varied with the number of crack rocks used in the past thirty days and years of use, which were each found to have a negative correlation with BDNF level. These results support the data produced by Corominas-Roso’s study (2012), and suggest that individuals are less likely to relapse if they exhibit higher levels of BDNF. Furthermore, this data suggests that the initial induction of BDNF protein expression as a result of cocaine intake (Graham et al. 2007) eventually becomes deregulated as a result of chronic exposure to the drug. This idea reconciles the varying effects which BDNF elicits depending on where it is injected into
the brain. Cocaine produces a widespread but temporary increase in BDNF expression in many areas of the brain, such as the VTA and nucleus accumbens, resulting in elevated cocaine-seeking behavior. This research provides a stronger understanding of the neurobiological mechanisms that surround addiction. One of the largest issues in this field is the ineffectiveness of treatment methods, as evidenced by high rates of relapse. The use of BDNF during the withdrawal period to determine the likelihood of relapse may provide an avenue for improved effectiveness of treatment methods and personal treatments tailored to individual drug users. With these potential benefits, this research would greatly assist addicts in understanding and overcoming their addiction and allow them to return to their normal lives.
The Fabric of Time and Space in the Hippocampus
orable events - the first day of school, our first kiss, the death of a loved one - to both a specific time and place. In fact, our lives seem inextricably tied to both a place and a time. Einstein, following this notion, describes us, humans, as something “limited in time and space.” These two dimensions are most fundamental to an experience: without one, an experience seems incomplete, and without both, an experience is nonexistent. As students of neuroscience, we are interested in how such experiences are recorded in memories. This year, the Nobel Prize in Medicine and Physiology was awarded to John O’Keefe for the discovery of place cells and to Edvard and May-Britt Moser for the discovery of grid cells. Place cells are cells found in the hippocampus, an area of the brain central to
Shivansh Chawla Writer
“A human being is part of a whole, called by us the ‘Universe’ —a part limited in time and space. He experiences himself, his thoughts, and feelings, as something separated from the rest—a kind of optical delusion of his consciousness.”-Einstein Through our lives, we attribute our most mem© 2015 Cornell Synapse
References: Corominas-Roso M, Roncero C, Eiro-Orosa FJ, Gonzalvo B, Grau-Lopez L, Ribases M, Rodriguez-Cintas, Sanchez-Mora C, Ramos-Qiorpga JA, Casas M (2012) Brain-derived neurotrophic factor serum levels in cocaine-dependent patients during early abstinence. Eur Neuropsychoparmacol 2012. D’Sa C, Fox HC, Hong AK, Dileone RJ, Sinha R (2011) Increasedserum brain-derived neurotrophic factor is predictive of cocaine relapse outcomes: a prospective study. Biol Psychiartry 70:706-711. Hillburn C, Nejtek VA, Underwood WA, Singh M, Patel G, Gangwani P, Forster MJ (2011) Is serum brain-derived neurotrophic factor related to craving for or use of alcohol, cocaine, or methamphetamine? Neuropsychiatr Dis Treat 7:357-364. Von Diemen L, Kapczinski F, Sordi AO, Narvaez JCM, Guimarães LSP, Kessler, FHP, Pfaffenseller B, de Aguiar BW, de Moura Gubert C, Pechansky F (2014) Increase in brain-derived neurotrophic factor expression in early crack cocaine withdrawal. International Journal of Neuropsychopharmacology 17:33-40.
5
Vol 9 | 2015
NEWS long-term memory, and they are activated whenever a mammal crosses a particular place (Moser, et. al 2008). Grid cells are cells found in patterns that help mammals keep track of their relative position. Together, these cells help form the brain’s “GPS” for memories.
Unfortunately, the hippocampus is vulnerable to cerebral vascular infarctions, or brain damage resulting from a lack of oxygen. If blood flow through carotid arteries is blocked for two minutes, through strangulation, hanging, or a heart attack, the CA1 section of the hippocampus, where place and time cells reside, starts to die (Kirino, 1982). Patients who experience a cerebral vascular infarction have impaired memory. Evidence elsewhere also points to the hippocampus’ keeping track of time: people with damage to the hippocampus can tell time accurately for only 20 seconds (Richards 1973). It is imperative to prevent these infarctions, for they can deprive patients of the ability to recollect essential human experiences. Place and time cell, the biological basis for memories, connect psychology, philosophy, and biology into a Recently, another class of cells, time cells, were found coherent framework. Our basic intuitions about memoto play a role akin to place cells (Eichenbaum, 2014). ries, experiences, and consciousness resonate with much In the words of the author, these cells, also found in of the biology in the brain. However, they fail to capture the hippocampus, do not fire in response to “external the complete picture. Deconstructing memories plays events, specific behaviors or spatial dimensions of an an important role in establishing the nature of our lives. experience,” but instead to temporal cues. These cells References: form the basis for the brain’s clock for memories. They Eichenbaum, H. (2014). Time cells in the hippocampus: A new dimension for mapping memories. Nature Reviews Neuroscihelp keep time, in grids similar to those of place cells. ence. If together, place cells and time cells can form complete Jacobs, N., Allen, T., Nguyen, N., & Fortin, N. (2013). Critical memories, if we let a memory be defined as an object in Role of the Hippocampus in Memory for Elapsed Time. Journal terms of place and time. Indeed, the hippocampus does of Neuroscience, 13888-13893. this in order to establish long-term memories. Specif- Kirino, T. (1982). Delayed neuronal death in the gerbil hippocam pus following ischemia.Brain Research, 57-69. ically, the hippocampus is most important in forming Moser, E., Moser, M., & Kropff, E. (2008). Place cells, grid cells, episodic memories, which are memories that Tulving and the brain’s spatial representation system. Annual Review of defined as a rich experience of place and time (Tulving, Neuroscience, 31(1), 69-89. 1985). The concept of episodic memory follows log- Richards, W. (1973). Time reproductions by H.M. Acta Psycho logica, 279-282. ically from the understanding of place and time cells. Tulving, E. (1985). Elements of Episodic Memory. Oup Oxford.
Caffeine: Alertness, Long-Term Memory, or Both? Joseph An Writer & Editor
Imagine taking a sip of piping hot coffee in an onthe-go cardboard cup, suited to full glory in a brown © 2015 Cornell Synapse
insulating sleeve. But now imagine that the acid flavor no longer contained the now-ubiquitous chemical known to boost alertness and shake off morning drowsiness. Coffee would cease to be anything like the “coffee” we know. Every year about 120,000 tons of the drug are consumed globally, enough to fuel one serving of a caffeinated drink to every single person in the world a day (Burchfield and Hopes 1997). It is a commonly known fact that caffeine increases arousal, vigilance, and processing speed. However, because of these broad-spectrum effects, it is difficult to focus on the 6
Vol 9 | 2015
NEWS
compound’s impact on the human body in controlled ways. Two main studies are considered here in order to understand the world’s most popular drug: the effect of caffeine in its ability to aid in long-term memory formation, and the physiological effects of caffeine in the human body, particularly in the central nervous system. Long-term Memory Consolidation Even though we know that caffeine generally induces cognition, its effect on long-term memory consolidation is unclear (Nehlig 2010; Borota et al. 2014). Past studies have yielded results indicating that caffeine has little to no effect on long-term memory formation. However, a recent study reveals that, to an extent, caffeine does indeed enhance long-term memory formation in humans. Dianel Borota et al. (2014) utilized a post-study design in which subjects were given images of objects to study. Subjects were soon after administered either 200 mg caffeine or a placebo pill. After 24 hours, subjects were given a recognition test and asked to indicate whether stimuli were targets (identical stimulus observed a day ago), lures (similar stimulus but not identical), or foils (completely dissimilar). Because caffeine tends to remain in the human system for over 24 hours, caffeine was expected to influence the consolidation of memories, or the transition of short-term memory to long-term. Subjects given placebo pills were expected not to have their memory formation function altered. The findings revealed that subjects who were administered caffeine had a higher likelihood of correctly calling lure items “similar” rather than “old” or “target”, and thus suggest that caffeine may in fact increase memory formation (Borota et al. 2014). The experiment also indicates that caffeine’s effect on long-term memory has a dose-dependency, but has an upper limit of 200 mg. The exact mode of caffeine’s neurological effect is still vastly speculative. Adenosine Receptor Antagonist Historically, the biochemical process by which caffeine induces alertness has been controversial, but now © 2015 Cornell Synapse
the general understanding is that caffeine has an antagonistic effect on extracellular adenosine receptors in the central nervous system (Basheer et al. 2004; Hayaishi et al. 2004; Porkka-Heiskanen et al. 2002; Fredholm et al. 2005; Satoh et al. 1996; Scammell et al. 2001; Hong et al. 2005). Normally, a molecule called adenosine binds to these receptors, inducing sleep and possibly the expulsion of toxins from the CNS (thus one reason why you need your sleep, all-nighter students!). Caffeine binds competitively to these receptors and mutes neurological pathways that induce drowsiness and sleep (Jinka et al. 2011). There are four G protein-coupled adenosine receptors (Fredholm et al. 2001) in question, and there is dispute over which receptors are antagonized by caffeine. Research shows that each receptor has a different purpose, and caffeine does not influence the function of all of them. There is still an ocean of information to be uncovered. Deeper knowledge regarding the mechanisms of caffeine action may help us find ways to possibly amplify the effects of caffeine while consuming smaller amounts, and reduce the undesirable side effects of caffeine use. The race to discover the mysteries of caffeine is spreading to other fields. For example, caffeine is being studied in species other than humans; honeybee memory capacity seems to improve after drinking nectar laced with caffeine (Wright et al. 2013) and the drug has been shown to reduce health due to neurodegenerative diseases in rodents (Cunha and Agostinho 2010). Discoveries about caffeine are arising often, but the full secrets of caffeine are unlikely to be unveiled anytime soon. References: Basheer, R., Strecker, R.E., Thakkar, M.M. & McCarley, R.W. Prog. (2004). Neurobiol. 73,379–396. Borota, D., et al. (2014). “Post-study caffeine administration enhances memory consolidation in humans.” Nature Neuroscience. 17, 201-203. Burchfield, G., Hopes, M., (1997).” What’s your poison: caffeine”. Australian Broadcasting Corporation. Retrieved 15 January 2014. Cunha, R.A. & Agostinho, P.M. J. (2010). Alzheimers Dis. 20(sup
7
Vol 9 | 2015
pl. 1), S95–S116 Fredholm, B.B., Chen, J.F., Masino, S.A. & Vaugeois, J.M. (2005). Annu. Rev. Pharmacol. Toxicol. 45, 385–412. Fredholm, B.B., Ijzerman, A.P., Jacobson, K.A., Klotz, K.N. & Linden, J. (2001). Pharmacol. Rev.53, 527–552. Hayaishi, O., Urade, Y., Eguchi, N. & Huang, Z.L. Arch. (2004). Ital. Biol. 142, 533–539. Hong, Z.Y. et al. J. (2005). Neurochem. 92, 1542–1549. Huang, Z. et. al. (2005). Adenosine A2A, but not A1, receptors mediate the arousal effect of caffeine. Nature Neuroscience. 8-5. pp. 858-859. Jinka TR, Tøien Ø, & KL, D. (2011). “Season primes the brain in
How Cannabis Consumption Affects the Brain Kamal Maher Writer
Everyone wants a better brain. The emerging topic of neuroplasticity is broadcast through many sources of media, from peer-reviewed scientific journal articles to advertisements claiming that games on the internet can improve your memory, focus, and learning skills. Neuroplasticity is based on the idea that the brain can repair or even enhance itself in the presence of either natural or controllable stimuli. A seemingly unrelated topic is the decriminalization of medical marijuana. As of June 20, 2014, the use of medical marijuana has been decriminalized in the state of New York. This news is becoming increasingly relevant to researchers across the nation due to one scientific phenomena: the active ingredient in marijuana (THC) actually stimulates neuroplasticity. The most important contributor to neuroplasticity is neurogenesis, the production of new neurons within the brain. Neurogenesis is now at the frontier of scientific inquiry after two recent events. The first event marks the discovery of neurogenesis within the adult brain. Prior to the 1990’s, researchers believed that the birth of new neurons occurred exclusively within the developing brain of infants. Within the past decade, however, scientists have observed neuronal growth within the adult brain as well. This discovery influenced several branches of research that examined the implications of neurogenesis, and the © 2015 Cornell Synapse
NEWS
an arctic hibernator to facilitate entrance into torpor mediated by adenosine A(1) receptors”. J. Neurosci. 31(30): 10752– 8.11.2011. Nehlig, A. J. (2010). Alzheimers Dis. 20 (suppl. 1) S85–S94. Ochiishi, T. et al. (1999). Neuroscience 93, 955–967. Porkka-Heiskanen, T., Alanko, L., Kalinchuk, A. & Stenberg, D. (2002). Sleep Med. Rev. 6,321–332. Satoh, S., Matsumura, H., Suzuki, F. & Hayaishi, O. (1996). Proc. Natl. Acad. Sci. USA 93, 5980–5984. Scammell, T.E. et al. (2001). Neuroscience 107, 653–663. Wright, G.A. et al. (2013). Science 339, 1202–1204.
conclusion was that it can be both good and bad. In a recent study published by Science, researchers at the University of Toronto identified two key factors in the function of neurogenesis. The first was that it occurs mainly within the hippocampus, the area of the brain that stores memories. Second (and more importantly), they discovered that the purpose of neurogenesis within the hippocampus is to regulate forgetting. The way neurogenesis works within the hippocampus is simply by replacement. Old neurons are replaced by new neurons. However, the problem is that the old neurons may have encoded memories that are essentially being wiped out by the new, blank neurons. Therefore, hippocampal neurogenesis actually causes forgetting. This becomes a problem when put into biological context. During a 2005 study published in The Journal of Clinical Investigation, researchers from across the globe collaborated to determine the effect of cannabinoids on the human brain. Cannabinoids, the family of neurotransmitters that includes THC, were found to stimulate hippocampal neurogenesis and forgetting, thus accounting for the typically characterized behavior of “stoners”. However, neurogenesis has also been located elsewhere in the brain, in places such as the cortex which is responsible for higher-level processing and problem solving. While it is thought that exercising this region of the brain through programs such as Lumosity may stimulate localized neurogenesis, numerous cannabinoid receptors have also been found in this region, leading researchers to believe that neurogenesis in those areas may be stimulated by cannabinoids as well. As a whole, these studies are currently inconclusive. Widespread restrictions on the study of THC preclude the scientific inquiries necessary for a better understanding of the chemical and its neuro8
Vol 9 | 2015
NEWS logical effects. While scientists and politicians alike hippocampus neurogenesis and produce anxiolytic- and antidestruggle with the ethics of THC, researchers contin- pressant-like effects. Journal of Clinical Investigation, 115(11), 3104-3116. doi: 10.1172/JCI25509 ue to struggle to make crucial discoveries in order to Scharfman, H. E., & Hen, R. (2007, 12). NEUROSCIENCE: Is find out whether it really can make our brains better. More Neurogenesis Always Better? Science, 315(5810), 336-338. References: Akers, K. (2014). Hippocampal Neurogenesis Regulates Forgetting During Adulthood and Infancy. Science, 344(6184), 598602. Retrieved October 16, 2014. Jiang, W. (2005, 12). Cannabinoids promote embryonic and adult
What Your Hometown Says about Your Future Health Brian LaGrant Writer & Editor
People at any given university come from all sorts of cities, towns, hamlets, and villages. Countless studies have shown that factors including size, population, and wealth all contribute to human development. However, a new study by neuroscientists has shown that hometown setting is related to the prevalence of dementia, a generalized type of cognitive decline. A study by Jia et al. (2014) focused on over 10,000 inhabitants of China over the age of 65. Overall, the researchers found that rates of dementia had increased significantly since 1980 from 3.1% to 5.1% of individuals over 65, which researchers attributed to increased life expectancies in the Chinese population. With recent advancements in medicine and knowledge about health, individuals are living longer and thus have a higher chance of developing a form of dementia. These individuals in the study came from 45 rural and 30 urban regions of China. The researchers interviewed the subjects and collected information on family history, lifestyle, and medical history before administering a series of neuropsychological assessments. These tests measured each subject’s verbal abilities and cognitive functioning. Each subject was classified as having dementia, © 2015 Cornell Synapse
doi: 10.1126/science.1138711
mild cognitive impairment, or no impairment at all. More surprisingly, the researchers also found that there was a significant difference in the prevalence of dementia by hometown. Proportionally, there were many more individuals with dementia in rural areas in comparison to urban areas. This difference, however, was not significant when accounting for differences in educational level between individuals in rural and urban areas. This phenomenon could be explained by the fact that being literate and pursuing further education, factors more prevalent in urban areas, have protective effects against the detrimental consequences of aging on the brain. However, those in urban areas had significantly higher incidences of vascular dementia, even after accounting for social class. Researchers suspect that this finding may be a result of stressful urban lifestyles: the constant rush, demanding work, and lack of sleep may contribute to the early onset of mental health problems. The results from the study by Jia et al. (2014) demonstrate that one’s hometown does play a significant role in health over time. It is also important to consider other factors such as education, stress, and access to medical facilities, for such factors can alleviate or exacerbate the negative cognitive effects that accompany aging. Through dissemination of data from this study and other similar studies in neuroscience, scientists are now able to better inform our current generation about the possible risk factors for mental health diseases. Reference: Jia, J., Wang, F., Wei, C., Zhou, A., Jia, X., Li, F., … Dong, X. (2014). The prevalence of dementia in urban and rural areas of China. Alzheimer’s & Dementia, 10(1), 1-9.
9
Call for Submisssion! cornell synapse 2016
For more information email us at cusn.synapse@gmail.com
Vol 9 | 2015
FEATURE Eliza-Baird Daniel Jane Wei Writer
Eliza Baird-Daniel is a senior from Washington studying Neurobiology in the College of Arts and Sciences. Her research interests include optogenetics, which is a neuromodulation method that uses light to control neuron excitation. Baird-Daniel works in the Goldberg lab, where she uses tools to demonstrate causation between signaling in an area of the brain stem and trial-and-error learning. Two to three times a week, in surgeries that can last six hours long, she implants lasers in finches, a process that allows her to see the firing of neurons in their brains. Baird-Daniel’s thesis is part of the Goldberg lab’s larger project of finding the root of trial-and-error learning using a songbird model. To illustrate the lab’s overarching research question, Baird-Daniel uses the example of a dartboard: as one gets closer to the bullseye, one is increasingly motivated to hit the target. The Goldberg lab’s research suggests that this comes from the ventral tegmental area (VTA) in the brain stem, which sends signals to the basal ganglia to aid in learning. Baird-Daniel says, “we have shown there is correlation; when a bird thinks it has done well, there is input from this structure.” However, she adds, “we need to show causation, which can be shown through electrical stimulation.” The problem is that electrical stimulation is not specific, since it is difficult to selectively activate neurons with this method. More evidence is needed to show a true cause-effect relationship. This is where Baird-Daniel’s work comes in. She is implementing the techniques of optogenetics in songbirds. Optogenetics, which involves genetically modifying neurons to exhibit light excitability, has been used extensively in mice but never in songbirds while they are actively singing. If implemented correctly, Baird-Daniel can add to the body of evidence that suggests causation. To carry out her experiments, Baird-Daniel introduces a viral vector that codes for channel rhodopsin, a light-sensitive protein generally © 2015 Cornell Synapse
found in the eye, into neurons in the finch’s brain. She also implants and activates a laser in the birds at specific syllables in their song, which can measure the firing of the neurons and allow for the observation of any differences. Baird-Daniel is still tweaking the factors involved to produce a bird that has both good viral expression and a successful laser implantation, which would allow her to identify the differences between stimulated and non-stimulated syllables. However, she has already shown that successful viral expression is possible in the structure of the bird brain that she’s working with. Baird-Daniel plans to apply her experience at the Goldberg lab to Weill Cornell Medical College, where she will work for a neurosurgeon specializing in seizure surgery. She hopes her experience with optogenetics can contribute to seizure prevention, noting that there are certain rhodopsin proteins that suppress instead of excite. “Making a net of inhibition around a seizure would be better than cutting out a sizable portion of the brain, which is commonly done for many seizures,” says Eliza. After her work at the Weill Cornell, she hopes to enter medical school and “see both ends of the pipeline” as both a doctor and a researcher.
11
Vol 9 | 2015
FEATURE Probing the “Actor and Critic” Model of the Songbird Learning System Eliza Baird-Daniel
Class of 2015, Dept. Neurobiology & Behavior, Goldberg Lab The songbird song system has proven to be a valuable tool in gaining understanding of the acquisition and development of motor skills. Birds learn to sing by gradually matching their vocalizations to a memory of a tutor’s song. Thus they provide a model of how learning occurs without external reinforcers such as juice or food—a closer approximation to how humans cultivate learned motor skills through trial-and-error as opposed many other animal models. One way to conceptualize how trial and error learning occurs is through the “actor and critic model”. This model hypothesizes that the song system is composed of certain structures that perform and drive motor output, the “actors”, and others that evaluate this performance, the “critics”. The robust nucleus of the archistriatum (RA), a song-related structure in the primary motor cortex, is an example of a likely “actor” although it has not been unequivocally confirmed. A likely candidate for a “critic” in the system is the ventral tegmental area (VTA)-- a dopaminergic midbrain structure. Here, I take multiple approaches in testing a functional model describing the neural mechanisms of trial and error learning. First, through building an optogenetic system, I attempted to test the “actor” role of the vocal motor cortex, RA, in song performance. Specific syllables were targeted for optical stimulation using real time song analysis. No significant difference was found between optically stimulated syllables compared to controls in both pitch and amplitude suggesting that optogenetics are not yet applicable to avian systems. Second, I used in vivo electrophysiological methods to chronically implant Microdrive recording arrays in the songbird ventral tegmental area (VTA). This area is associated with reward in many systems and thus is a good candi© 2015 Cornell Synapse
date to provide an internal reward signal. Implantation site was determined through antidromic identification. This was achieved through the implantation of a stimulation electrode in the VTA- receiving part of the basal ganglia and recordings in VTA. These procedures allowed for the evaluator role of dopaminergic inputs into the basal ganglia to be tested during song performance. Lastly, I used neuroanatomical tracing techniques to identify an anatomical pathway that explains how VTA receives information regarding ongoing song quality. A combination of dextran and herpes simplex viruses (HSV) were used to distinguish a novel pathway that could provide temporal information regarding song output to the evaluation system. Taken together, these findings shed light on the functional roles of evolutionarily conserved pathways that drive trail land error learning.
Fig. 6 A) A model of my proposed pathway through which temporal information reaches VTA through RA-DMP-VP (represented in pink). B) Schematic showing injection sites and retrograde identification of DMPMMAN , DMPVP , and VPVTA C) Presence of 555-labeling from Tomato in MMAN (5X magnification) D) Coincidence of 555-labeled cell body and 488-labeling in DMP (20X magnification) E) Dark field image showing location of DMP F) 647-retrogradely labeled VPVTA neuron and 488-labeled collaterals from DMP (40X magnification). White arrow shows possible connection site. G) Retrogradely 488-labeled cell body found in RA (20X magnification) 12
Vol 9 | 2015
FEATURE Katarina Cheng Zach Griffin Writer
Katarina Cheng is a fourth year student majoring in Biological Sciences with a General Biology concentration in the College of Arts and Sciences. Cheng first began her involvement with the Schaffer-Nishimura Lab when she met a graduate student who was working on the imaging of cytomegalovirus-infected mice. Cytomegalovirus is a common virus found amongst humans, but it rarely manifests itself in symptoms, because it is typically dormant. The negative effects of cytomegalovirus are frequently seen in people who are immunocompromised, such as HIV patients. The virus can also trigger adverse effects during childbirth if the mother has contracted the virus during pregnancy. If the mother is a disease carrier during the gestation period, the fetus may receive the pathogen, which has the potential to be fatal. These topics are highly pertinent to Cheng’s research. She has been working in the immunology and biomedical engineering field for the past three years under Dr. Bryan Rudd, researching the immunological responses of newborns with the virus. Her goal is to discover where the virus localizes in the brain and when the virus is most actively replicated during pregnancy. Cheng works primarily with the graduate students in her laboratory. Her independent research focus is the cytomegalovirus, but she also works with different cells in the brain producing retinoic acid, which is a metabolite that the body needs to grow and develop properly. So far, she has found that the virus is localized around the choroid plexus, a network of vessels and ventricles in the brain that produces cerebrospinal fluid and removes metabolic waste and foreign materials. This fact hints that the virus encapsulates the brain during development by means of cerebrospinal fluid infection. In the future, she hopes that her research will serve as a stepping-stone to provide a window of opportunity for other scientists to discover treatment possibilities for those affected. Cheng enjoys working with her colleagues in the laboratory because of their strong teamwork and con© 2015 Cornell Synapse
stant communication with each other. Her Principal Investigator frequently conducts his own experiments, providing insight into areas of the field she normally wouldn’t be able to see. Her graduate student advisor has served as a useful mentor both inside and outside of the lab, helping to bridge the gap between her research, her schoolwork and her social life. Cheng’s experience in research allowed her to learn about the subject of immunology before even taking classes, which facilitated her learning in the classroom. It has also helped to demonstrate that her studies can be applied in the real world. She hopes to further her studies in medical school after this year, where she hopes to get involved in translational immunology research or clinical outcomes research by becoming a neonatal surgeon. Despite her commitment to her laboratory, Cheng is actively involved in multiple endeavors on and off campus. She serves as the Co-President of the Cornell Elderly Partnership, where she coordinates weekly visits to the Cayuga Ridge Skilled Care Facility, Clare Bridge Nursing Home and Sterling House. Cheng is also a Student Advisor in the Office of Undergraduate Biology, where she mentors younger Cornell students in her field of study. As an undergraduate teaching assistant for the three-credit course BIOPL 1120, Cheng led weekly discussion sections and evaluated oral presentations and writing assignments. During her spare time, she enjoys photography, hiking, and swimming around Ithaca.
13
Vol 9 | 2015
Patterns of retinoic acid production in the neonatal brain after cytomegalovirus infection
Katarina Chang
Class of 2015, Dept. Neurobiology & Behavior, Rudd Lab Introduction: In healthy adults, cytomegalovirus infection rarely causes symptoms. However, congenital CMV infection of the developing human central nervous system can result in permanent brain damage and neurological impairment, including congenital deafness, and vision and cognitive impairment. It is the most prevalent viral infection among infants in the developed world, affecting 30,000-40,000 newborns annually in the United States alone. The mechanism of infection trafficking into the developing brain and subsequent pathogenesis are unknown. Previous work conducted in the Rudd Laboratory observed preferential expression of CCR9 on CD8+ T-cells in the neonatal brain after murine CMV infection. Retinoic acid (RA) has been established as a key modulator of CCR9 up-regulation on gut CD8+ T-cells. We hypothesized that RA presence in the brain may have a similar role in lymphocyte trafficking into the brain in the context of MCMV infection. Methods: Pathogen-free newborn mice were infected with murinc CMV at birth. At 7, 14, 17, 21, and 28 days
FEATURE post-infection, infected and uninfected neonatal brains were harvested. Populations of brain CD8+ T-cells, macrophages, dendritic cells, B-cells, natural killer cells, and levels of RA production were quantified using flow cytometry. Coronal organotypic brain sections were imaged using confocal microscopy to identify physical locations of RA production. Results: Examination of RA production levels demonstrated significantly elevated RA levels in the brains of MCMV-infected neonates, notably in the choroid plexus. Macrophages were primarily responsible for RA production, and maximal levels of RA production by macrophages occurred at 17 DPI, the peak of the CD8+ T-cell response. Discussion: The choroid plexus is a key source RA production in the developing brain, and influences optimal blood brain barrier (BBB) development. Based on the association of RA and CCR9 upregulation, our own prior observations of preferential expression of CCR9 on CD8+ T-cells present in the brain following infection, and current conclusions of elevated RA levels in the choroid plexus of infected mice, RA levels in the choroid plexus may influence CCR9-mediated homing of CD8+ T-cells through the BBB. The results of this study suggest aberrant retinoic acid production in the brain after neonatal MCMV infection may contribute to the resulting neurological sequelae.
80
Brain-Control Brain-MCMV
60
Figure 6: MCMV-gB infected mice show significantly elevated levels of ALDH1 activity compared to uninfected controls until 21 DPI
40 20
28
21
17
14
0 7
Percent of Lymphocytes
ALDH1+ Populations in the Brain
DPI
Š 2015 Cornell Synapse
14
Vol 9 | 2015
FEATURE Wei-Feng “Aaron” Lee Nicole Levine Writer
Wei-Feng “Aaron” Lee is a third year undergraduate majoring in Human Development in the College of Human Ecology. He has extensive research experience that dates back to his first year at Santa Monica College in California, where he conducted research on how resilience affects perceived attractiveness in a social context. Lee continued to develop his research interests when he spent one summer at Harvard University studying the differences in the neural pathways that form memories. When Lee applied to Cornell, he was drawn toward Cornell’s Human Development major, because it appeared to be an interdisciplinary field that coupled psychology and neuroscience with practical skills. At Cornell, Lee soon learned about Professor Charles Brainerd’s work in the Department of Human Development and became particularly interested in his guiding beliefs about research. “No matter what research you do,” Lee summarized, “you must have an empirical question; something to be tested.” Lee’s research deals primarily with memory, which we can broadly categorize into two forms: gist and verbatim. Gist memory refers to “fuzzy representations” of previous occurrences that are based on the implications of facts, in which gaps of known information are filled in with assumptions. Conversely, verbatim memory consists of hard facts and details of past events. Phantom recollection occurs when a person remembers something based on gist memory, whereas recollection rejection occurs when a person is certain that an event did not happen because he or she is aware of its absence. Professor Brainerd’s laboratory is focused on false memory phenomena. When a person recollects a memory that did not actually happen, he or she has produced a false memory. More specifically, the primary topic of Lee’s thesis explores the relevance of time in the formation of false memories. With the guidance of graduate student Carlos Gomes, Lee has found that false memory exists when gist memory can correctly fill in the necessary gaps, while verbatim memory is used when detailed facts are necessary. © 2015 Cornell Synapse
Beyond the science, false memory has broad implications for our society. For example, the creation of false memories from gist memories is commonplace amongst youth who testify in court when they are unable to accurately remember a traumatic event. False memories are also commonplace amongst elderly people who are particularly susceptible to neurodegenerative conditions such as Alzheimer’s Disease. Lee’s research experience has taught him how to take initiative and become a better scientist. “Cornell has the resources to help you do whatever you want to do,” he said. His favorite part about doing research is questioning and testing tentatively accepted hypotheses about how the mind works. As of now, Lee is uncertain about what he plans to do in the far future, but he would like to apply his problem-solving skills to find creative solutions to “questions that matter.” When not in the laboratory, Lee works at the Career Exploration Center and enjoys playing soccer and writing fictional stories. During his spare time, he likes to spend time with his friends in his apartment and partake in light-hearted debates with them. 15
Vol 9 | 2015
Time Course of False Memory Processes Aaron Lee
FEATURE quantified. In this study, we investigated the time course of each retrieval parameter to test theoretical predictions about false and true recognition. Specifically, we hypothesized that false memory would decrease with response deadline due to an increase in recollection rejection.
Class of 2015, Dept. Neurobiology & Behavior, Brainerd Lab
Methods: 164 undergraduates were presented with 72 DRM lists Introduction: composed of four words each for either 1s or 5s, and then False memory – when people remember something received a recognition test in which subjects had either that did not actually happen – is frequently studied 750ms, 1500ms, or 6000ms to respond to a test probe. via a word list paradigm called Deese-Roediger-McDermott (DRM; Roediger & McDermott, 1995). In Results: the DRM, subjects are presented with lists of semanAcross all other variables, the acceptance rate of tically associated words (note, sound, piano, sing) fol- new related words (i.e., false recognition) decreased lowed by a recognition test composed of studied words significantly with response deadline. Furthermore, the (sound), new related words (music), and new unre- conjoint recognition model used – with goodness-oflated words (fish). This allows the computation of the fit values of 11.74, 12.02, and 3.79, all lower than the bias-corrected acceptance rate of studied words (true critical value of 15.51 – showed a steady increase in recognition) and new related words (false recognition). recollection rejection as response deadline increased. The fuzzy-trace theory (Reyna & Brainerd, 1995) posits that subjects store representations of the surface Discussion: form of studied items (verbatim traces) as well as the We suggest that the decrease in false memory with rebottom-line meaning of them (gist traces). According trieval time is due to recollection rejection, which supports to the theory, false memory is suppressed by verbatim rejection of related words via verbatim traces of studied traces and supported by gist traces. Using a mathemat- words (e.g., “I did not study music because I remember ical model called conjoint recognition, three retrieval seeing note, sound, piano, and sing instead”). More speprocesses for new related words (recollection rejection, cifically, it is likely that the longer retrieval time allowed phantom recollection, and similarity judgment) can be subjects to better utilize surface traces collected earlier.
Figure 1: The estimates of each retrieval process according to response deadlines (i.e., retrieval time) obtained using the mathematical model.
© 2015 Cornell Synapse
16
Vol 9 | 2015
FEATURE Nicholas Petersen Sanjna Surya Writer
Nicholas Petersen is a fourth year student majoring in Biological Sciences with a concentration in Neurobiology and Behavior. His initial involvement in neuroscience research began somewhat coincidentally. It was by chance that Petersen rode in the same bus as Laura Manella, his former TA in introductory neuroscience. Shortly after, Petersen shadowed Manella as she performed experiments on neural firing rates in the olfactory bulbs of rats, which are the brain structures involved in the sense of smell. He currently works in Dr. Christiane Linster’s lab conducting experiments to extend Manella’s findings. Petersen implants electrodes in the rat’s olfactory bulbs and stimulates the bulb by infusing it with norepinephrine, the neurotransmitter and hormone that partakes in the fight-or-flight response. He then measures changes in neural firing patterns to understand the role norepinephrine plays in modulating spontaneous firing rates and odor evoked signal-to-noise ratios. Petersen’s experiments thus far have produced interesting results. He has discovered that both high and low concentrations of norepinephrine can decrease rat neuron firing rates by 5-10 Hz; however, moderate concentrations can have unpredictable consequences on firing rates. Petersen hopes to use these findings to explain the enhanced abilities of rats to detect low odor concentrations and discriminate between similar odors at both low and high concentrations of norepinephrine. Such a finding would help researchers understand the role of the neurotransmitter in olfactory processing. Additionally, these types of experiments are critical to uncover the mechanisms underlying the least understood sensory system of humans, the olfactory system, which has close ties to neural processes like learning, memory and alertness. Petersen has found the applicability of science to be a valuable component of his research experience thus far. More specifically, his favorite part about working in a laboratory is the “hands-on experience” – the ability to use his hands to perform delicate surgeries and precise experiments. © 2015 Cornell Synapse
Outside of the laboratory, Petersen is also minoring in Fine Arts and has been particularly interested in installation sculpture, as evidenced by his sculpture of a floating brain displayed in the hall of the neurobiology department at Corson-Mudd Hall. Integrating his passion for neurobiology and art, Petersen is also the Director of MEDART under the MEDLIFE program, where he plans and implements art projects with elderly residents suffering from impairments such as Alzheimer’s disease and dementia. His experience in research, the fine arts and MEDART have provided him a budding domain expertise in this field. After graduation, Petersen plans to conduct clinical research in the field of neurological disorders such as ALS (Amyotrophic Lateral Sclerosis), which is a neurodegenerative disease that damages nerve cells in the central nervous system. Ultimately, he intends to matriculate into medical school. As he admits, his rat surgeries have not only equipped him with skills for the medical field but also made him less queasy. In his words, that is “always useful for a doctor.” 17
Vol 9 | 2015
Noradrenergic Modulation of Spontaneous Mitral Cell Activity in the Olfactory Bulb of Anesthetized Rats
Nicholas Petersen
Class of 2015, Dept. Neurobiology & Behavior, Linster Lab The main olfactory bulb (MOB) receives dense noradrenergic projections from the pontine nucleus of the locus coeruleus (LC), which has been shown to modulate olfactory behaviors such as odor discrimination and detection. More specifically, noradrenergic modulation in the olfactory bulb is thought to enhance the signal-to-noise ratio of odor stimuli. In my present study, I utilize in vivo electrophysiology in adult rats to investigate the effects of norepinephrine (NE) on MOB cellular processing. In particular, I measure changes in
FEATURE
spontaneous firing rates and firing patterns in MOB mitral cells (MCs) after local infusion of NE in anesthetized rats. I also investigate the effects of selective adrenergic receptor subtype activation (α1, α2, and β) viainfusion of NE with two of three selective antagonists (1000μM NE with prazosin-α1 antagonist, yohimbine-α2 antagonist, or alprenolol-β antagonist). Overall, NE decreased MC spontaneous firing in a dose dependent manner. Interestingly, changes in firing rate depended on the initial frequency – low initial frequency MCs mostly increased in firing rate after NE infusion and high initial frequency MCs mostly decreased. The overall variability of MC frequency also robustly decreased after NE infusion. Moreover, NE significantly increased MC spontaneous spike synchrony in a majority of MC pairs. Both the suppression of MC firing and enhancement of synchronous spiking are likely mediated by the α2 receptor. Thus, I provide a possible neural mechanism underlying noradrenergic modulation of the signal-to-noise ratio in olfactory behavior.
Figure 1. (A) Mitral cell identification. Recorded units were classified as mitral cells when the pattern of activity was “respiration locked”. In other words, firing activity (middle trace) corresponds to respiratory behavior (upper trace). The lower trace shows the mean frequency analogous to the to spike train (middle trace).(B) Schematic representation of infusion needle and electrode placement. © 2015 Cornell Synapse
18
Vol 9 | 2015
FEATURE Roshansha Singh Mary Abramczuk Writer
The ability to recognize odors is important to many species, including humans. But how are olfaction and memory connected? Roshansa Singh is an undergraduate neuroscience researcher who conducts research in this area. Singh, a fourth year student from Edison, New Jersey, is pursuing a Biological Sciences major in the College of Arts and Sciences. She researches in the Computational Physiology lab, which is supervised by Dr. Thomas Cleland from the Department of Psychology. In her current position, she works directly with her lab partner, Christian Martinez, and her graduate supervisor, Michelle Tom. Her research focuses on learning and memory through odor representation, particularly olfaction in mice, through the process of “generalization.” Generalization, Singh explained, takes place when we associate similar odors. We can often recognize scents as belonging to broad categories, such as citrus, but we can still differentiate between individual kinds of citrus smell, such as orange and lemon. Singh’s research studies how the similarity of one odor to another affects memory in mice. First, the mice are taught that sand infused with a certain scent contains a buried food reward. Once they learn to dig for the reward, they are presented with sand infused with compounds that differ from the familiar scent by varying degrees, and their digging behavior is observed. Singh hypothesizes that the less similar a scent is to the reward-associated scent, the less digging the mice will do. The lab also studies the effects of the inhibitor K252a, a compound that inhibits a TrkB receptor in the brain called Brain-Derived Neurotrophic Factor (BDNF). BDNF is known to play a role in both odor representation and memory, so inhibiting it reduces the mice’s ability to remember a scent. Various aspects of the receptor are being studied, including its role in longterm memory and the difference between mice who are born without BDNF and those in whom BDNF is © 2015 Cornell Synapse
merely inhibited by K252a. This quest to understand the neural systems responsible for memory and olfaction is part of science’s ongoing attempt to decipher the workings of the brain, and could have important applications in memory-related diseases such as Alzheimer’s. The most rewarding parts of research, Singh says, are pursuing independent, hands-on learning and meeting other people who are enthusiastic about neuroscience. Being involved in research has also helped her become more adaptable; she credits the older researchers she’s worked with for teaching her how to adjust and perfect experimental procedures while preserving the integrity of the experiment. When she is not in the laboratory, Singh is involved with the Red Cross and has served as Treasurer for the Cornell Undergraduate Research Board (CURB), a student organization that promotes the undergraduate research experience on campus. She is also a brother in the Alpha Phi Omega national service fraternity and the Co-President of REACH, a program dedicated to tutoring children grades K-12 in various academic subjects. She enjoys playing Ultimate Frisbee in her spare time. After graduating from Cornell, Singh intends to matriculate into medical school and simultaneously pursue a career in clinical research. 19
Vol 9 | 2015
The role of the TrkB-BDNF pathway in associative and non-associative olfactory behavior
FEATURE
similar odors, with increasing similarity to conditioned odor resulting in greater investigation time.
Results: The vehicle group habituated as expected with a sigRoshansa Singh nificant difference between Hab1 and Hab4 and the Class of 2015, Dept. Neurobiology & Behavior, mice were able to significantly discriminate between the Cleland Lab habituated odor and a test odor. The K252a group, however, failed to habituate, with no significant changes in Introduction: Brain-derived neurotrophic factor (BDNF) and investigation time with repeated presentation of the haits receptor, tyrosine receptor kinase B (TrkB), play a bituated odor. Importantly, on Hab4, investigation times significant role in learning and memory in the olfac- for the drug and vehicle groups differed significantly. In tory bulb. Here, we utilize K252a, a TrkB antagonist, STM, both vehicle and drug groups correctly recognize during an associative and a non-associative olfactory conditioned odor and dig in it the most. Despite a genbehavioral task. Non-associative mechanisms of olfac- eral decrease in digging time with decreasing similarity tory memory have been localized to the OB whereas from the conditioned odor, the atypicality of the vehiassociative mechanisms have shown to employ long- cle group proved further analysis of the data difficult. term, higher processing. Through our study, we aim to develop a better model for the role of acute BDNF Discussion: As non-associative mechanisms are localized to the deficit in the OB as it relates to odor representation. bulb, we expected and saw OB antagonists of TrkB receptors to alter spontaneous discrimination. Alternatively, Methods: We utilized two behavioral tasks: spontaneous dis- associative tasks are multimodal in nature and K252a crimination and short-term generalization (STM). has shown to have long-term effects on memory, leading Spontaneous discrimination measures the ability to the prediction that few differences would be seen in of mice to habituate to repeated presentation of an the vehicle and drug groups in STM. Future studies with odor and non-associatively discriminate between STM should try to better establish the effects of K252a. novel odors. STM, on the other hand, is a reward- In sum, the BDNF-TrkB pathway is critical in shaping ed behavioral task that measures the extent to which memory during non-associative olfactory tasks and may mice are able to generalize a conditioned odor to be a significant player in long-term associative memory.  Figure 2. Spontaneous discrimination. The vehicle group habituates, decreasing investigation time with each successive odor presentation, while the drug group fails to habituate. A T-test measured significant difference between Hab1 and Hab4, only for vehicle. The vehicle group is able to discriminate between habituated (Hab 4) and test odor (S1), while drug cannot. Both groups had relatively high investigation times. Š 2015 Cornell Synapse
20
Vol 9 | 2015
FEATURE Nathan Sklar Sarah Park
Writer Adult zebra finches are commonly found birds in Central Australia – so prevalent that they are colloquially described as the potato chips of the Outback, because “you can never just have one.” These are the finches that senior Nathan Sklar has grown fond of through his research. Sklar has always been interested in biology, but it was not until the summer after his second year of college that he was able to channel his passion into a research position. Prior to starting, Sklar underwent an initial training that taught him how to catch birds that have run away. “If the lights are turned off, the finches will stop moving. Then, if you wrap the finches’ heads between your two fingers and apply light pressure on their shoulders, they will naturally squirm into your hand.” Sklar’s work has since progressed rapidly since his training. He initially worked under a graduate student studying the role of the nonapeptide vasopressin in the behavior of voles. Sklar is now examining the role of a related nonapeptide, called vasotocin, in the behavior of zebra finches. Both nonapeptides are involved in the pair-bonding behavior of the sexually monogamous zebra finch. They manipulate behavior by affecting the dopamine-controlled reward felt by the animal when it partakes in a particular activity—in this case, being with its mate. What is the relationship between dopamine and vasotocin? Would increasing the presence of vasotocin in zebra finches cause them to favor being with their partner? Before determining the direct answer to this question, Sklar wanted to understand how finches would behave without nonapeptide manipulation. The initial experiment itself was deceptively simple; the most complex equipment Sklar used consists of no more than colored construction paper and a few cages. To create the set up, Sklar constructed a cage with two compartments: one compartment was wrapped with paper of one color, the other with paper of another. They were separated with a removable partition. On day one, he placed a zebra finch into one side of the cage for 15 minutes. The next day, at the same time, he put the same zebra finch and its partner into the other side of the cage for 15 minutes. © 2015 Cornell Synapse
Sklar repeated this process for four more days. On the seventh day, Sklar removed the partition and placed the finches in the cage. The finches could choose which side to go to; in this first set of tests, the finches chose to spend 95% of the first 5 minutes on the side where they had been with their partners. The finches had developed what is called a conditioned place preference, in which the conditioned stimulus was associated with a reward. As described previously, these results were obtained before Nathan began any neurological manipulation; the noted behaviors were indicative of how the birds naturally act. At the time of this interview, which occurred in the early stages of the experimental process, Sklar indicated that he did not want to rush to conclusions regarding the implications of the study. “If I were to be hyperbolic, I could say that [vasotocin is] a love potion for birds. In fact, there are analogous nonapeptides in humans that have already been established. It is interesting to observe how social bonding works in other animals.” Regardless of the neuroscience behind the phenomenon, the behavior of birds indicate they are fond of their partners; some even sang when they were on their partner’s side of the cage. This suggests that humans and birds may have similarities in their fundamental neurological workings and expressions of happiness.
21
Vol 9 | 2015
A Test of the Organizational Effects of Arginine Vasotocin and V1aR Antagonist on Conditioned Place Preference for Reunion with Pair Partner in Adult Male Zebra Finches
Nathan Sklar
Class of 2015, Dept. Neurobiology & Behavior, Adkins-Regan Lab Introduction: Aspects of pair bond formation across species have been viewed as resembling a kind of addiction, but the process of bond formation is much more complex than most forms of addiction. Arginine vasopressin (AVP) and the related molecule arginine vasotocin (AVT) are thought to modulate social behavior in many different taxa through the social behavior network. This social behavior network shares much of the same brain regions with the mesolimbic reward system, which employs dopamine (DA) to select for behaviors that increase an organism’s survival. These two systems likely interact to produce the full range of an organism’s social bonding behaviors, but the nature of their interaction is not fully understood. Also not fully understood is the mechanism of a recently suggested organizational effect of AVT in social organisms. This experiment addresses both of these problems using the zebra finch, a songbird that forms pair bonds for life. These pair bonds are correlated with both pair maintenance behaviors such as clumping and dopamine release from the mesolimbic reward pathway, suggesting a reinforcement of pair maintenance behavior. Early life AVT modulation has also been shown to have a quantifiable effect on the zebra finch brain and behavior throughout development, which implies lifelong organizational effects on the social behavior network. If this change also affects the mesolimbic reward pathway, we hypothesize that those birds who receive additional AVT early in life should remain closer to their pair partners and show a stronger preference for specific place in a conditioned place preference (CPP) trial as adults, while those that receive an antagonist for vasopressin receptor 1a (V1aR) should display opposite effects.
FEATURE onist called Manning compound (MC), or saline as a control. These subject birds were then allowed to pair with a wildtype conspecific for at least two weeks, after which they were conditioned to prefer one side of a cage using contact with the pair partner as the stimulus. The conditioned subjects were then run through a conditioned place preference (CPP) test, and their preference for one side of the cage was recorded. Results: In the CPP trials MC birds spent less time with their pair partners during the first reunion trials and developed less conditioning than AVT or control birds. However, the data gathered were too bimodal and the sample size was too small for the findings to be significant. Conclusion: While the results were inconclusive, they suggest that the hypothesis of a connection between modulation of the social behavior network and modulation of the reward associated with pair interactions is worth further testing.
Table 1: Conditioning of subject zebra finches across treatment groups. As can be seen below, 4 out of 6 Methods: control birds, 3 out of 7 AVT birds, and only 1 out of 5 Eighteen zebra finch males were injected intracra- MC birds displayed conditioning. Despite the trend in nially with either Arginine vasotocin, a V1aR antag- these data, statistical tests proved non-significant. 22 Š 2015 Cornell Synapse