Bookmark and Share
|
  • Text +
  • Text -

Neuroscience

Click to watch Gabriel Friedman '12 discuss his research project.

Acute Stress and Immune Function

Anjali Cera ('12); Kaitlyn Casimo ('13); Arielle Snagg ('13); Nick Lawson ('14); Gabriel Friedman ('12); Kunwei Song ('12); Caitlin Plefka ('13); Roxanna Salim; Mentor: Nicole Weekes, Richard Lewis

Abstract: Acute and chronic stress have differing effects on immune function. Chronic stress tends to lead to poor health outcomes.  Acute stress leads to overall immune enhancement and immunoprotection as evidenced by increases in leukocyte mobilization.  This indicates that both the length of a stressor and the perceived duration of a stressor play pivotal roles in stress induced modulations of immune function. While the effects of chronic stress on immune function have been heavily researched there is significantly less work examining the effects of acute stress. In this study each subject’s perception and experience of the stressor will be examined in conjunction with immune function.  To evaluate immune function at multiple time points throughout this study we will measure three salivary markers: cortisol, C-reactive protein, and salivary immunoglobulin A.  Differences in stressor perception/experience should be predictive of changes in these immune markers.  During summer 2011 we tested 9 subjects in order to further investigate these issues.
Funding Provided by: Pomona College SURP  

Identification of Novel Contributors to Axon Guidance in Drosophila

Steven Chau ('12); Mentor: Karl Johnson

Abstract:  Understanding how nervous systems utilize chemical cues to guide growing neurons has been a central interest of developmental biologists. Although the major molecular role players in Drosophila melanogaster have been identified in the attractive Netrin/Frazzled system and the repulsive Slit/Robo system, it is likely that some modulatory or downstream components still remain unidentified. Here we outline an exploratory forward genetic screen of 15 deficiency mutants designed to identify such contributors and provide evidence of one possible novel molecule.     The 6965 stock, along with the other 14 deletion mutants to be screened, has no known deficiencies in previously-documented guidance molecules. Via immunohistochemistry and embryonic dissections, we show that 6965 homozygotes present with a mild phenotype involving fascicle defects and so suggest the existence of a molecule that interacts with the Slit/Robo pathway.
Funding Provided by: Rose Hills Foundation  

HSPGs Regulate Slit Distribution in Drosophila

Meredith Course ('12); Mentor: Karl Johnson

Abstract:  Secreted factors help guide developing axons to their proper synaptic targets.  The distribution of one of these factors, Slit, is regulated by heparan sulfate proteoglycans (HSPGs). The HSPGs Syndecan (Sdc) and Dallylike (Dlp) share the same carbohydrate polymer backbone and HS sidechains, but have disparate localization patterns and mutant phenotypes. Mutations in sdc diminish Slit-mediated repulsion at the midline, while mutations in dlp show genetic interactions with Slit in lateral fascicle formation. Loss of Dlp alters Slit distribution distal but not proximal to the midline, suggesting that a distinct yet overlapping pattern of HSPG expression provides a spatial system that regulates axon guidance decisions. Here, we explore the mechanism by which Slit is distributed, as well as the different roles of Sdc and Dlp in Slit distribution.
Funding Provided by: Elgin Fund (MC) National Science Foundation ARRA Grant #IOS-0841551 (KJ)

The Role of Synbindin on Synapse Development at the Neuromuscular Junction

Rachel Ekaireb ('12); Mentor: Karl Johnson

Abstract:  Syndecan, a Heparan Sulfate Proteoglycan, is crucial in Drosophila nervous system development. Syndecan has been shown to promote growth of the neuromuscular junction, and it has been hypothesized that binding partners of sdc's highly conserved cytoplasmic domains act as downstream effectors. My project focuses on elucidating the function and localization of proposed binding partner, Synbindin. Drosophila larva lacking Synbindin in muscle tissue have significantly smaller synapses and cannot emerge from their pupal cases. A Myc-tag was inserted adjacent to the coding sequence of Synbindin and this construct was injected into flies. The synbindin-myc fly line was crossed with 24B-Gal4 flies, driving synbindin-myc expression in muscle. Synbindin doesn’t appear to localize to the neuromuscular junction. Furthermore, over-expression of Synbindin does not affect synapse size, and loss of synbindin does not significantly affect syndecan localization. Future experiments with Synbindin-HA tag constructs will provide further insight into Synbindin’s function and interaction with Syndecan.
Funding Provided by: Pomona College SURP  

Regulation of Gonadotropin-Releasing Hormone Neurons: Kisspeptin-GPR54 Signaling and Inhibition by RFamide-Related Peptide-3

Jennifer Franks ('12); Tal Dror ('13)*; Matt Poling*; Josh Kim*; Azim Khan*; Sheila Semaan*; Sangeeta Dhamija*; Mentor: Sasha Kauffman*
*University of California San Diego,  Reproductive Medicine Dept,  San Diego, CA

Abstract:  GnRH has been shown to play a critical role in the neural control of fertility in animal models and humans. Specifically, GnRH neurons are necessary to generate the luteinizing hormone (LH) surge responsible for ovulation. Administration of kisspeptin, a product of the kiss-1 gene, increases LH levels in mice and kisspeptin’s receptor, GPR54, is colocalized with GnRH neurons. Also, RFRP-3, a mammalian neuropeptide, inhibits GnRH firing in mice and RFRP releasing neurons may directly innervate GnRH neurons. In this study we used GPR54 knock out mice to assess the necessity of kisspeptin-GPR54 signaling in the generation of the pre-ovulatory LH surge. We also used RACE to analyze the untranslated regions of the RFRP gene. Our results suggest that kisspeptin-GPR54 signaling is necessary for evocation of an LH surge and that there are alternative transcription start sites for RFRP transcription that can result in two different RFRP RNA isoforms.
Funding Provided by: Claremont Colleges  Neuroscience Fellowship Program  

The Cognitive Effects of MusicLearning in Low-socioeconomic Settings

Gabriel Friedman ('12); Mentor: Nicole Weekes

Abstract:  Childhood socioeconomic status shapes neural development and influences neurocognitive performance, especially in areas related to language and executive function. At the same time, music learning has been shown to induce specific neurological developments and enhance cognitive functioning. This study investigated whether a short-term music intervention could enhance the IQ of children raised in low-socioeconomic environments. 30 subjects were randomly assigned to one of two groups – the experimental group that received musical training and the control group that served as a waitlist control.  The 15 subjects in the experimental group received piano lessons for 4 weeks and received a keyboard to practice on daily. I.Q. testing occurred both pre- and post- 4 week training in both groups. Results suggest that a short-term music intervention is associated with a small, but measurable, increase in IQ.
Funding Provided by: Aubrey H. and Eileen J. Seed Student Research Fund Donald A. Strauss Public Service Scholarship Foundation 

Treating Genetic Mutations with Antibiotics: A Preliminary Study

Alex Groth ('12); Mentor: Jonathan Matsui

Abstract:  Usher Syndrome 1B (USH1B) is a genetic disorder resulting in profound deafness and blindness in humans. The zebrafish mariner mutant exhibits the same premature stop codon mutation present in the Myosin7a motor protein responsible for USH1B in humans. Scientists have shown that aminoglycoside antibiotics decrease DNA translation accuracy resulting in read-through of premature stop codons in human kidney cell lines, thereby creating previously absent proteins.  Here, in preparation for treating mariners, we administered different concentrations of the aminoglycoside gentamicin to zebrafish larvae that express green fluorescent protein in their sensory hair cells. We fixed the larvae and imaged the sensory hair cells to determine if gentamicin was toxic to hair cells and the larvae. We found that 50 µM gentamicin was a safe dosage to treat developing zebrafish without high mortality rates. We will characterize the vision of the mariner mutant and then treat the mariner mutant with gentamicin.
Funding Provided by: Paul K. Richter and Evalyn E. Cook Richter Memorial Fund (AA) National Institute of Health Grant #R15DC010998-2  (JM) 

Light Treatment Causes Damage to the Retinas of Hypopigmented Zebrafish

Kelsey Jensen ('12); David Davila ('12); Mentor: Jonathan Matsui

Abstract:  Unlike mammals, zebrafish (Danio rerio) are capable of regenerating damaged retinas.  The adult albino mutant zebrafish retina lacks melanophores making it prone to light damage and is an animal model to study retinal cell death and regeneration.  Little is known about how light treatment affects larval zebrafish, but using larvae would reduce the time needed to conduct experiments.  We raised ruby mutants, a double albino mutant strain that also lacks iridophores, in normal and constant light conditions. We stained larvae with acridine orange to quantify the levels of cell death in the retina. We used the optokinetic response behavioral assay at 5 and 6 days post-fertilization to measure visual function in control and light-treated ruby mutants.  Preliminary results indicate that hypopigmented larvae have higher levels of cell death and worse vision than wild-type larvae raised under constant light conditions.  Therefore, rubys are a good animal model to study retinal damage.
Funding Provided by: Pomona College SURP (KJ) National Institute of Health Grant #R15DC010998-2  (JM) 

Sex Differences in Spatial Learning Using the Ziggurat Task

Ilona Kats ('12); Connie Wu ('13); Xin Wang ('13); Mentor: Jonathan King

Abstract:  Studies have shown sex differences in spatial learning tasks. Male rats have been shown to make fewer errors on the Morris water maze and the radial arm maze although some findings are contradictory. Different strategies in navigation (geometric vs landmark cues) could account for some of the differences in performance. In the current study we assessed behavioral differences in rats by using a dry land maze, the ziggurat task.  We also measured long term potentiation (LTP) in the hippocampus. Our results show that males were significantly faster at finding the baited ziggurat.  Males also made significantly more errors than females.  This could be due to the fact that males also obtained the food significantly more often while the females appeared not to be searching.  LTP was also different between sexes, females displayed more potentiation than males. Overall, our study shows that there are sex differences in spatial learning and LTP.
Funding Provided by: Pomona College SURP  

Co-Treatment with Retinoic Acid Causes a Partial Rescue of the Fetal Alcohol Syndrome Phenotype in Zebrafish (Danio rerio)

Jonas Kwok ('13); Phillip Uribe; Mentor: Jonathan Matsui

Abstract:  Fetal alcohol syndrome (FAS) occurs when mothers consume alcohol during pregnancy and affects thousands of live births in the United States, 90% of which have ocular defects, including microphthalmia (small eye).  One hypothesis is that ethanol disrupts retinoic acid (RA) signaling mechanisms during development.  In recent studies, some features of FAS in zebrafish larvae were rescued by co-treatment with RA.  Beginning at 48 hours post-fertilization, we treated wild-type zebrafish larvae in 1% ethanol and/or 10-9 M RA in order to assess the possible “rescue effect” RA has on microphthalmia and cell death.  We measured ratios of eye area to body length to characterize microphthalmia and quantified the levels of cell death in the retina using the acridine orange stain.  Preliminary data indicate that, like ethanol, RA alone induces microphthalmia and increases the numbers of dead cells in the retina, but that co-treatment ameliorates both effects.
Funding Provided by: National Institute of Humanitites  (JT)  

Elucidating Functional Domains for Drosophila Syndecan Localization

Jereen Kwong ('12); Margaret Nguyen ('10); Mentor: Karl Johnson

Abstract:  Heparan Sulfate Proteoglycans (HSPGs) are important for axon guidance at the midline and synapse formation at the neuromuscular junction (NMJ).  Previous experiments suggest that the core protein of Syndecan may be involved in synapse formation at the NMJ. In this project, we seek to identify the domains important for Sdc function by building Sdc constructs lacking specific domains and testing for their localization and rescue ability at the NMJ.  Overexpression of various constructs in muscle cells produced the following results: (1) SdcFL localized to the synapse postsynaptically, (2) SdcY-F, SdcDC2, SdcDcyto, and SdcDC1 localized to the synapse postsynaptically, but they were also found in vesicles within muscle cells.  (3) Sdc-cyto was distributed throughout the cytoplasm.  These data suggest a model in which the cytoplasmic domain may participate in trafficking Sdc to the cell surface. Once there, the ectodomain may be involved in localizing Sdc to the synapse.
Funding Provided by: Norris Foundation  

White Matter Abnormalities in ADHD Subjects and their Siblings

Katherine Lawrence ('12); Owen Phillips*; Katherine Narr*; Jennifer Levitt†; Mentor: Katherine Narr*
*Laboratory of Neuro Imaging (UCLA); †The Jane and Terry Semel Institute for Neuroscience and Human Behavior, Geffen School of Medicine (UCLA), University of California Los Angeles, CA

Abstract:  Previous voxel-based and regions-of-interest-based diffusion tensor imaging (DTI) studies have found decreased fractional anisotropy (FA) and increased mean diffusivity (MD) in ADHD subjects, though findings remain relatively mixed. We used refined tractography methods on DTI data to examine FA, MD and tract volume of the arcuate fasciculus, anterior thalamic radiation, cingulum, corticospinal tract, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, forceps major, forceps minor, superior longitudinal fasciculus and uncinate fasciculus in children and adolescents with ADHD (n=61), unaffected siblings of ADHD probans (n=33) and demographically similar healthy controls (n=15). While we found no significant FA differences between ADHD subjects and controls, ADHD subjects showed significantly increased MD in the anterior thalamic radiation, forceps minor, right inferior longitudinal fasciculus, left inferior fronto-occipital fasciculus and right superior longitudinal fasciculus, and a smaller tract volume of the left inferior fronto-occipital fasciculus relative to controls. Unaffected siblings of ADHD subjects displayed similar differences in MD.
Funding Provided by: Claremont Colleges Neuroscience Fellowship Program  

Group Differences in Stress, EEG Prefrontal Asymmetry and Health

Kun-Wei Song ('12); Arielle Snagg ('13); Caitlin Plefka ('13); Kaitlyn Casimo ('13); Anjali Cera ('12); Gabriel Friedman ('12); Nick Lawson ('14); Roxanna Salim; Mentor: Nicole Weekes, Richard Lewis

Abstract:  Our current study is a continuation of previous research investigating sex differences in depression and prefrontal asymmetry using EEG. Evidence suggests that there are definite sex differences in clinical depression. One theory explaining this difference is that women experience more stressors and demonstrate greater sensitivity to them than do men. Stressor reactivity has been measured using both EEG and cortisol. Additional evidence suggests that prefrontal asymmetry may serve as a risk factor for both clinical depression and depressive states. Sex differences have also been observed in the relationship between EEG asymmetry and emotional reactivity and between EEG asymmetry and depression. 40 subjects were previously tested. Correlations were observed between EEG asymmetry and depression. However, sample sizes were insufficient to investigate sex differences. In order to rectify this issue of statistical power, we have tested an additional 10 subjects during the summer of 2011, and will continue testing in the fall.
Funding Provided by: Pomona College SURP  

Zebrafish Inner Ear Sensory Hair Cells Respond to Gentamicin in a Dose-dependent Manner

Kevin Wang ('13); Mentor: Jonathan Matsui

Abstract:  The sensory hair cells found in the inner ear die when humans are treated with the aminoglycoside gentamicin, leading to permanent hearing loss. Most studies using aminoglycodies in zebrafish (Danio rerio) have focused on hair cells found in the lateral line and not in the inner ear. We characterized the ototoxic effects of gentamicin on hair cells found in the utricle, one of the inner ear balance organs. We treated adult GFP-Brn3c transgenic zebrafish, whose hair cells express green fluorescent protein, with varying concentrations of gentamicin. Zebrafish heads were removed and fixed. Utricles were extracted, imaged, and hair cell counts performed to create a dose-response curve.  Increasing concentrations of gentamicin resulted in fewer hair cell densities in the utricle, indicating that gentamicin is an effective method to induce hair cell death.
Funding Provided by: Pomona College SURP (KW) National Institute of Health Grant #R15DC010998-2  (JM) 

Sex Differences in Spatial Learning Using the Ziggurat Task

Connie Wu ('13); Ilona Kats ('12); Xin Wang ('12); Mentor: Jonathan King

Abstract:  Studies have shown sex differences in spatial learning tasks. Male rats have been shown to make fewer errors on the Morris water maze and the radial arm maze although some findings are contradictory. Different strategies in navigation (geometric vs landmark cues) could account for some of the differences in performance. In the current study we assessed behavioral differences in rats by using a dry land maze, the ziggurat task.  We also measured long term potentiation (LTP) in the hippocampus. Our results show that males were significantly faster at finding the baited ziggurat.  Males also made significantly more errors than females.  This could be due to the fact that males also obtained the food significantly more often while the females appeared not to be searching.  LTP was also different between sexes, females displayed more potentiation than males. Overall, our study shows that there are sex differences in spatial learning and LTP.
Funding Provided by: Pomona College SURP  

 


 

Research at Pomona