This REU site is now closed. Our 3 years of NSF funding ended in 2018. There will be no further applications accepted.
Summer 2017:
Faculty Mentor: Surendra Ambegaokar, PhD Ohio Wesleyan University
This project focuses on how certain genes may regulate aspects of both neuronal growth and neuronal health. In particular, the role of microRNA-7 (miR-7) will be studied in human neural progenitor cell lines (SH-SY5Y). This cell line is derived from a human glioblastoma, and miR-7 expression is also related to cancer in many other non-neuronal cell types. Previous research has found changes in miR-7 expression during brain development. Students in my lab will continue previous work on measuring the expression of miR-7 before, during, and after neuronal differentiation. This project will also transfect SH-SY5Y cells to alter the expression of miR-7 to examine the effects on neuronal differentiation. Reduced expression of miR-7 also reduces neurotoxicity due to the protein Tau, which is highly related to Alzheimer disease and other neurodegenerative disorders. Students will have the ability to continue research on the molecular interaction between miR-7 and Tau. This project will allow training in a variety of molecular and cellular techniques, namely maintaining mammalian cells in culture, RNA and miRNA purification, and quantification of RNA via quantitiative PCR (qPR).
Faculty Mentor: Christian G. Fink, PhD Ohio Wesleyan University
Epilepsy affects roughly 1% of the world’s population [1], with approximately 10% of these people being effectively treated by surgical removal of an epileptic focus [2]. This approach is a method of last resort when anti-epileptic drugs are ineffective, since removing a portion of a patient’s brain may have undesirable side effects. In this project we will theoretically investigate the feasibility of preventing seizure propagation by severing a few individual connections from an epileptic focus, rather than removing the focus in its entirety.
We will explore this idea by running simulations of epileptic seizures using a recently developed theoretical model of seizure dynamics [3], as well as the connectivity map of the macaque brain [4]. The question we seek to answer is: how can we identify which neural connection(s) should be removed in order to best inhibit seizure propagation? We will use tools from dynamical systems theory and network theory to formulate quantitative measures to answer this question.
This project will therefore involve developing a computational model of the macaque brain in order to model the propagation of epileptic seizures. After learning about fundamental techniques in computational neuroscience, students will write code in Python to run these large-scale simulations. Overall, the project is appropriate for any student with experience in differential equations and computer programming, and who has an interest in computational neuroscience.
REFERENCES
[1] Thurman et. al. “Standards for epidemiologic students and surveillance of epilepsy,” Epilepsia, 2011.
[2] Surgery for Epilepsy, NIH Consensus Statement, 1990 Mar 19- 21; 8(2):1-20.
[3] Jirsa et. al. “On the nature of seizure dynamics,” BRAIN, 2014.
[4] Modha and Singh. “Network architecture of the long-distance pathways in the macaque brain,” PNAS, 2010.
Faculty Mentor: Grit Herzmann, PhD College of Wooster
The Herzmann lab investigates the neural mechanisms of how humans are able to perceive faces, memorize visual material, and remember this material later on. The research focuses especially on cases of superior performance as found in face processing of own-race faces. Research shows that all people are better at learning and remembering faces from their own-race as compared to a different race. Understanding how perception and memory is improved for own-race faces can be translated into training programs for people suffering from learning disabilities or dementia. REU participants will use event-related brain potentials (ERPs) to measure brain activation while participants perceive, memorize, and recognize faces. Participants will be involved in study design, stimulus choice and preparation, data collection, and literature review. Participants will be able to experience a large part of the experimental process of human neuroscience research from conception to setup to data collection.
Faculty Mentor: Harry Itagaki, PhD Kenyon College
The enteric nervous system (ENS) is the part of the peripheral nervous system associated with the digestive tract. In vertebrates, the ENS has as many neurons as the spinal cord, but what we understand is just a tiny percentage of what is known of other parts of the CNS and the PNS. As the gut and its microbiota are increasingly implicated in overall health and behavior, it is imperative that we start to gain a better understanding of the ENS. Using insect models, the aims of this project are to look at the expression of different neurotransmitters and neuromodulators in the ENS, investigate their physiological effects, and assess their interactions with diet and gut microbiota.
Faculty Mentor: Beth Mechlin, PhD Earlham College
The Mechlin lab examines the relationships between stress and health, since chronic stress can negatively impact health in a variety of ways (McEwen, 1998). Projects in the Mechlin lab focus on causes of stress and pain in human participants. Summer studies may include examining how using apps to practice mediation or gratitude influences physiological stress responses, and investigating how various factors influence pain sensitivity. REU participants working on this project will be involved in participant recruitment, data collection, data entry, and data analysis. They will learn how to administer psychosocial questionnaires, measure blood pressure and heart rate, collect saliva for cortisol measures, administer a social stress test, and administer a cold pain test. REU participants will have the opportunity to add measures to the protocol to test their own hypotheses (for example, a previous student added a measure of perfectionism).
Faculty Mentor: Sarah Peterson, PhD Kenyon College
The Petersen lab investigates the genetics of developing nervous systems, including the myriad interactions of neurons, glial cells, and their environments. We are particularly interested in the development of the myelin sheath, which is formed by specialized glial cells to surround and protect axons in the central and peripheral nervous systems (CNS and PNS). To answer our questions, we use the zebrafish model system, which has become a premiere genetic model organism for myelination (D’Rozario, Monk, and Petersen, 2016). Recently, a large-scale forward genetic screen at Washington University in St. Louis uncovered a number of zebrafish mutants with reduced terminal differentiation of glial cells. We are characterizing a subset of these mutants in the Petersen lab to understand how the affected gene normally regulates nervous system development. One of our mutants has severe patterning defects, including deficits in axon guidance and neural crest cell migration. Initial genomic analysis suggests this phenotype is due to aberrant muscle patterning, highlighting the coordinated development of multiple PNS cell types with other organ systems. Other mutants have phenotypes restricted to either CNS or PNS myelin, suggesting a specific role of the affected gene in myelinating glial cells. REU participants would have the opportunity to phenotypically characterize mutants in order to discover when (stage) and where (cell type) nervous system development is affected. In addition, computational analysis of whole genome sequencing data can uncover candidate causative mutations in these strains. REU participants may be trained in zebrafish husbandry, vertebrate CNS and PNS neuroanatomy, genetics and genomics, phenotypic characterization and expression analysis via in situ hybridization, and in vivo live imaging.
Faculty Mentor: Bob Rosenberg, PhD Earlham College
In humans, spinal cord injury causes life-long paralysis. But when spinal cords of lamprey (a primitive vertebrate fish) are cut, the neurons recover from the injury, regrow, and reconnect. Within 10-12 weeks, the animals swim normally again. The over-arching goal of this research is to determine the roles of sodium channel expression during regeneration of lamprey spinal cord neurons. This line of research could contribute to new knowledge that eventually leads to improved treatment of devastating spinal cord injuries.
Our hypothesis is that expression of voltage-gated sodium channels is decreased in lamprey spinal cord neurons following spinal cord injury. Voltage-gated sodium channels are required for electrical signaling in neurons (action potentials), but excess activation can cause hyperexcitability and cell death. We have preliminary evidence that lamprey neurons survive trauma better than those in higher vertebrates because they down-regulate sodium channel expression. This evidence is from immunofluorescence microscopy, in which voltage-gated sodium channels are labeled with specific antibodies and then visualized with fluorescent secondary antibodies. Axons with high levels of sodium channel expression are significantly fewer in number in regenerating spinal cords than in uninjured spinal cords. In addition, we have preliminary evidence that chronic inhibition of sodium channels during the recovery period accelerates the recovery of swimming ability.
Students working on this project will learn techniques in small-animal survival surgery, spinal cord dissections, biological tissue fixation, cryosectioning, immunofluorescence labeling, fluorescence microscopy, image quantification, computational image analysis, and small-animal behavioral assays. Additional techniques may include Western blot, ELISA (enzyme-linked immuno-sorbent assay), and electrophysiological recordings of resting and action potentials. Students will work together as a group while they learn the techniques, and then each student (or pair of students) will choose a sub-project to focus on for the remainder of the summer.
Faculty Mentor: Amy Jo Stavnezer, PhD College of Wooster
The Stavnezer lab is currently testing the impact of hormonal manipulations across the lifespan on the learning and memory in rodents. An exciting and still unanswered area of research surrounds the neurobehavioral and cellular influence of hormone replacement therapy on aged females. Female rats that receive an ovariectomy followed by a mid-range tonic estrogen treatment demonstrate improved spatial working memory ability (Mennenga et al., 2015), however, treated aged ovariectomized rats do not improve in spatial reference memory (Talboom et al., 2008). In addition the majority of these rodent data have been collected on virgin female rats despite the fact that 75% of women will give birth. REU participants will learn surgical procedures, hormone injections, behavioral assessment of activity, spatial learning, working and reference memory, and histology of various brain regions using cell body stains, immunocytochemistry and cell counts to help address these questions. In addition, we will work with data sets from previously completed experiments on hormone, environmental disruptors and strain differences in rodent behavior. A strong understanding of statistics will assist in working on those particular projects. Lastly, the lab is taking on a new research challenge to assess the ability of frequency specific microcurrent on pain, healing or possibly as treatment in a rodent model of attention deficit disorder. The participants will become familiar with the literature and procedures and then determine an avenue of hormone study or microcurrent research for their own project.
Summer 2016:
Faculty Mentor: Surendra Ambegaokar, PhD
Location: Ohio Wesleyan University, Delaware, OH
The Ambegaokar lab explores how genes regulate two important neuronal cellular processes– RNA translation and autophagy in Drosophila. We are investigating a mechanism (which undergraduates were involved in discovering) of negative feedback between microRNA-7 and a RNA-binding protein, hnRNP K, in co-regulating important signaling cascades in neurons, e.g. insulin receptor pathway, and the epidermal growth factor receptor pathway. Also of interest is the common “background” gene in Drosophila – white – which may induce autophagy in addition to providing pigmentation to eyes. All three genes also alter neurodegenerative phenotypes in Drosophila, and participants could test if these genes also affect neuronal susceptibility to infection by the neuron-specific Sigma virus, which only infects insects. Sigma virus infection also induces a unique behavioral response that causes paralysis when exposed to high doses of carbon dioxide (CO2) (L’Heritier, 1948). Given the importance of CO2 detection in fruit flies, my lab is using Sigma virus and this unique phenotype to better elucidate the CO2 sensory pathway in Drosophila. REU participants will integrate several techniques to approach these questions, including subcloning of genes, RNA immunoprecipitation, RT-qPCR, Western blots, transfection of human cell lines (e.g. human embryonic kidney cells, or SH-SY5Y glioblastoma cells), stereoscope & scanning electron microscope imaging of “rough” eyes and other neural-related morphology, immunofluorescent microscopy, and simple behavioral assays to measure motor function in flies. This research will train participants in many fundamental concepts and several techniques employed in molecular neuroscience.
Faculty Mentor: Kira Bailey, PhD
Location: Ohio Wesleyan University, Delaware, OH
The Bailey lab is testing the hypothesis that action video games (AVGs) can be used to modify the neural correlates of cognitive control. The significance of this work lies in the implication that the skills acquired in an AVG might be transferred to other contexts (Boot et al., 2011; Green et al., 2009) which is in contrast to findings from a wealth of training paradigms wherein improvements in performance transfer very narrowly (to highly similar tasks) or not at all. Establishing a causal relationship between AVGs and behavioral and neural changes requires carefully designed training studies. The proposed research seeks to conduct a rigorous training study to address the methodological shortcomings in previous work and provide a more thorough investigation of video game effects on executive functioning and perceptual ability, using a combined behavioral and psychophysiological approach with latent variables. REU participants will use event-related brain potentials to measure the neural correlates of cognitive control measured in one or more of several tasks (e.g., Stroop, Flanker, AX-CPT) they choose to associate with their research question before and after participants undergo 20 hours of AVG training.
Faculty Mentor: Andrew Engell, PhD
Location: Kenyon College, Gambier, OH
The Engell lab uses electroencephalogram (EEG), event-related potentials (ERPs), and behavioral paradigms to investigate the “social brain”: those brain areas that support perception of socially relevant stimuli such as emotional face expressions, gaze shifts, biological motion, and underlying social competencies such as the inference of another’s goals and intentions. Face perception, a highly developed visual skill vital to typical social processing, represents an ideal model system for advancing our understanding of the social brain. The extremely complex processes that support face perception are belied by the speed and ease with which we detect and identify faces, read facial expressions, interpret gaze direction, etc. The Engell lab will investigate the nature and timing of the neural processes that make such complex tasks feel so effortless. Interestingly, brain regions thought to be critical for face processing are co-localized with regions thought to be critical for other social competencies such as the perception of bodies (Weiner & Grill-Spector, 2013; Engell and McCarthy 2014) and biological motion (Bonda et al., 1996; Engell & McCarthy 2013). The lab is thus also interested in understanding the extent of functional overlap of these systems. REU participants would be trained in the acquisition and analysis of scalp–recorded EEG and ERPs to investigate some combination of these issues.
Faculty Mentor: Grit Herzmann, PhD
Location: The College of Wooster, Wooster, OH
The Herzmann lab investigates the neural mechanisms of how humans are able to perceive faces, memorize visual material, and remember this material later on. The research focuses especially on cases of superior performance as found in experts like birders or car experts (Herzmann & Curran, 2011; Tanaka & Curran, 2001). These people, because of extensive perceptual learning, are better able to perceive and memorize stimuli of their expertise (Bukach et al., 2006). Understanding how perception and memory is improved in these cases can be translated into training programs for people suffering from learning disabilities or dementia. REU participants will use event-related brain potentials to measure brain activation while participants perceive, memorize, and recognize faces. Participants will be involved in study design, stimulus choice and preparation, data collection, data analysis, and literature review. Participants will be able to experience the whole experimental process of human event-related potential research from setup to write up.
Faculty Mentor: Seth Kelly, PhD
Location: The College of Wooster, Wooster, OH
The Kelly lab aims to better understand the control of gene expression during nervous system development by focusing on how a family of RNA binding proteins regulates gene expression during axonal pathfinding and overall nervous system functioning. Mutations in ZC3H14, one member of this family, have been identified in a small number of intellectually disabled human patients. We began to investigate the function of the evolutionarily conserved Drosophila homolog of ZC3H14, called Nab2 that appears to be required for axon pathfinding in the fly CNS (Kelly, 2015). Projects in the lab will use immunofluorescence and other molecular techniques to further characterize pathfinding defects observed in Nab2 mutants and other pathfinding mutants in the lab. As a corollary to these projects, our lab is also interested in understanding how defects in pathfinding (in several different fly mutant strains) are related to changes in fly behaviors such as learning and memory, sleep, and circadian rhythm. In sum, these experiments should provide REU participants with strong training in the fields of neuroscience, cell biology, and genetics.
Faculty Mentor: Hewlet G. McFarlane, PhD
Location: Kenyon College, Gambier OH
The McFarlane lab investigates behaviors in mouse models of mental illnesses and correlates these to the brain chemistry of the subjects. Most of the work is done in the BTBR T-tf/J mouse, an excellent model for autism (McFarlane et al., 2008). Work ongoing in our laboratory suggests that in addition to the behaviors observed that model Autism spectrum disorder symptoms, these mice are interesting in a variety of additional ways. For example, BTBR mice are more aggressive than controls. This behavioral finding needs to be further investigated given that some reports suggest low levels of aggression in this strain (Silverman et al, 2010) while others suggest otherwise (Pobbe et al., 2010). A wide variety of behaviors are assessed (motor, cognition, emotional); brain chemistry is assessed using high performance liquid chromatography with electrochemical detection (HPLC-ED). REU participants could expand on this ongoing work using a behavioral pharmacological approach. Participants could assess baseline aggression using a resident-intruder paradigm and attempt to modulate the behaviors using a variety of drugs that are active in the central nervous system. Depending upon their interest, they could also further pursue the relevance of different neurotransmitters in production of autism-like behaviors.
Faculty Mentor: Beth Mechlin, PhD
Location: Earlham College, Richmond, IN
Please note that this research position will run on a different timeframe: from May 9 – July 1. Please be sure you can commit to the entire 9 weeks before choosing this research position.
The Mechlin lab examines the relationships between stress and health, since chronic stress can negatively impact health in a variety of ways (McEwen, 1998). Projects in the Mechlin lab focus on causes of stress and coping strategies. Current studies include examining the impact discussing paying back debt has on the physiological stress response, testing a new iPhone app to see if expressing gratitude decreases stress, and investigating the impact exposure to a specific wavelength of light has on pain sensitivity. REU participants working on this project will be involved in participant recruitment, data collection, data entry, and data analysis. They will learn how to administer psychosocial questionnaires, measure blood pressure and heart rate, collect saliva for cortisol measures, administer a social stress test, and administer a cold pain test. REU participants will have the opportunity to add measures to the protocol to test their own hypotheses (for example, a previous student added a measure of perfectionism).
Faculty Mentor: Jennifer Yates, PhD
Location: Ohio Wesleyan University, Delaware, OH
Animal models of acute spinal cord injury (SCI) have indicated that long-term outcome depends on both direct mechanical damage (in humans, this might come from a car accident or sports injury) and delayed secondary pathologic mechanisms (cellular events that happen AFTER the initial injury that make damage worse). The Yates lab investigates the role of macrophages (a subtype of inflammatory immune cells) in this secondary tissue damage and delayed loss of motor and sensory function by using the guinea pig SCI model (Yates et al., 2006 & 2014). Oxidative stress and neurotoxicity are two distinct cellular mechanisms of secondary damage, and they are currently treated with methylprednisolone (MP) and quinolinic acid (QUIN) blockade, respectively. REU participants will use surgical, behavioral, and immunohistological methods to test several potential research questions to further understand these cellular processes. Participants might test the hypothesis that treatment of acute SCI with short-term MP and long-term QUIN blockade will lead to additive effects on functional recovery and tissue preservation. Instead, they may work on a dose response measurement of the QUIN blockade or optimize the staining and quantification of QUIN in injured tissue.