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Identifying novel contributors to axon guidance at the Drosophila melanogaster midline

Dane Brodke (2013); Mentor(s): Karl Johnson

Abstract: In bilaterally symmetric animals, developing axons in the CNS follow molecular guidance cues to reach their targets. Some of these molecular systems have been well-characterized in Drosophila including the attractive Netin/Frazzled system and the repulsive Slit/Robo system. Modulatory and downstream components of these systems remain unidentified. We aim to identify some of these components by the use of a forward genetic screen, whereby mutants are screened for defects and the mutations are mapped on the genome to find the gene responsible for a defect. The 8941 stock has shown the most potential with regards to the identification of a novel contributor to axon guidance. Embryos of this stock have midline crossing defects whereby axons cross the CNS midline in error. The 7537 deletion, which overlaps the 8941 deletion, causes a similar defect. The 23164 deletion, which also overlaps the 8941 deletion, does not have the defect. These results indicate a narrow region of interest for the gene deletion causing the defect. Within this region, the deletion of the gene spenito is likely to be causing the defect. Further experiments will test this hypothesis.
Funding Provided by: Fletcher Jones Foundation; National Science Foundation - IOS-0841551

Examining the Function of Drosophila Syndecan’s Cytoplasmic Domain

Naomi Wagner (2013); Additional Collaborator(s): Margaret Nguyen; Mentor(s): Karl Johnson

Abstract: Syndecan (Sdc) is a transmembrane heparan sulfate proteoglycan that promotes synapse growth at the Drosophila neuromuscular junction (NMJ). We are studying the cytoplasmic domain of Sdc (SdcCD) in order to better understand its specific function at the NMJ. Past lab students built Sdc constructs lacking all or part of the cytoplasmic domain, and we are currently testing these constructs in gain-of-function assays in order to determine how SdcCD contributes to Sdc’s localization at the NMJ. Our results indicate that, without the complete cytoplasmic domain, Sdc is trapped within the cell’s secretory pathway and cannot properly localize to the synapse. In addition, we seek to identify binding partners for SdcCD. Five candidate interactors have been identified. Our goal is to confirm these protein-protein interactions using an in vitro binding assay, the GST pulldown. Our results thus far indicate that three of the interactors – Cora, Ced-12, and eIF-4a – bind to SdcCD.
Funding Provided by: Koe Family; National Science Foundation - IOS-0841551

Ginsenoside Metabolite Rd Modulates Synaptic Plasticity in the Rat Hippocampus

Connie Wu (2013); Student Collaborator(s): Genesis Resendiz (2013); Xin Wang (2013); Mentor(s): Jonathan King

Abstract: Ginseng has long been touted to enhance cognitive performance. Ginsenosides Rg1 and Rb1 (prevalent in Panax ginseng) have been used to rescue performance in cognitive tasks and increase hippocampal excitability. Although these studies suggest a link among ginsenosides, learning, and synaptic plasticity, there remain inconsistencies regarding their effects. Because ginsenosides are metabolized in the body, studying its metabolites may further elucidate the mechanisms behind its effects. Our study examined the dose-dependent effect of ginsenoside Rd (metabolite of Rb1) on synaptic plasticity in rat hippocampal slices. Our results show a significant increase in basal responses in 5nM and 25nM Rd treatments compared to control. Concentrations of 5 and 25nM Rd produced paired pulse inhibition while 50nM Rd produced paired pulse facilitation. Additionally, Rd has a dose-dependent enhancing effect on LTP. Thus, Rd and perhaps other metabolites of Rb1 have the potential to act as modulators of synaptic plasticity.
Funding Provided by: Sherman Fairchild Foundation (CW, XW); Kenneth T. and Eileen L. Norris Foundation (GR)

Understanding developmental dyslexia in Cantonese-speaking children: a study of event-related potentials and components associated with lexical processing

Sean Pianka (2014); Student Collaborator(s): Jinghua Ou†; Sylvia Kwok‡; Andrew Au* (Graduate Student); Additional Collaborator(s): I-fan Su*; Dustin K.Y. Lau‡ Mentor(s): Sam-Po Law*
*The University of Hong Kong; †The Hong Kong Polytechnic University; ‡Hong Kong Institute of Education

Abstract: Understanding neural correlates of developmental dyslexia in Chinese-Cantonese speakers requires investigations sensitive to the logographic dynamics of Chinese characters. This study utilized event-related potentials recorded during a lexical decision task to explore patterns of neural activation among Hong Kong primary school children of poor and typical reading ability. The task required participants to distinguish between Chinese characters appropriate to their education level and pseudocharacters that obey orthographic rules of character form but are not present in the Chinese lexicon. Real characters with pronunciations identical to their phonetic radical were classified as regular words, while those that differed in tone or pronunciation were classified as irregular words. Analysis of event-related potentials focused on the N170, P200 and N400 waveform components. The data showed that among typical readers irregular words elicited greater N170 amplitude in the parietal-occipital region than regular words, and that pseudocharacters elicited greater N400 amplitude in the frontal-central region than real characters. These findings indicate that in typical readers relationships of regularity affect the initial recognition and analysis of learned characters, and that unfamiliar characters elicit greater neural activation in later stages of lexical processing. This suggests that deficits in radical awareness hinders the ability of poor readers to decode characters.
Funding Provided by: The East Asia Grant

Testing the Prenatal Androgen Theory of Homosexuality and Transgender Identity

Danie Diamond (2015 SCR); Student Collaborator(s): Alexis Takahashi (2013); Zach Schudson (2013); Christina Beijjani (2013); Mentor(s): Rachel Levin

Abstract removed upon request.

Beyond the Binary: Sexual Fluidity and Hormone Therapy in the Trans* Population

Alexis Takahashi (2013); Student Collaborator(s): Zach Schudson (2013); Mentor(s): Rachel Levin

Abstract removed upon request.

Searching for Regulators of the HPA Axis in Major Depression Patients: A Preliminary Genotyping Screen

Patrick Liu (2014); Additional Collaborator(s): Heather Ryan*; Mentor(s): Greer Murphy*
*Stanford University

Abstract: Major depressive disorder (MDD) is a common disorder with lifetime prevalence rates as high as 17% in the United States. Studies over the past several decades have consistently shown that overactivity of the hypothalamic-pituitary-adrenal (HPA) axis is linked to MDD, but the biological mechanisms underlying this irregularity is still unclear. To better understand these mechanisms, we are performing a genome wide association study (GWAS) which focuses on the hypothesis that increased dopamine activity, secondary to HPA over-activity, can lead to psychotic symptoms in MDD. This focus gives us the unique opportunity to target specific genes of the HPA axis and dopamine system and to test their association with the occurrence of psychotic symptoms in patients. Here, we report the workflow and results of our genotypic screen in which we selected 7 candidate genes and genotyped 22 single nucleotide polymorphisms (SNPs) of psychotic major depression patients (n=32), non-psychotic major depression patients (n=32), or healthy individuals (n=40). With the future completion of the clinical study, a principle component analysis will be carried out to test the association of the genes of the HPA axis and dopamine system with the incidence of specific psychotic symptoms and with other measures of the disorder.
Funding Provided by: National Institute of Mental Health; The Department of Veterans Affairs; NARSAD; Organon, Inc.

Conserved mechanism of phagocytosis in mammals and Drosophila

Christina Bejjani (2013); Student Collaborator(s): Stephanie Valdez (2013); Mentor(s): Junryo Watanabe

Abstract: Macrophages are professional phagocytes of the mammalian immune system. They adjust their surface receptors and secreted products in response to environmental cues and local stimuli. Classically activated macrophages, M1 macrophages, perform antimicrobial functions and secrete proinflammatory cytokines. In contrast, alternatively activated macrophages, M2 macrophages, are involved in mechanisms such as tissue regeneration and release antiinflammatory cytokines. Macrophage-mediated clearance of apoptotic debris is crucial for regeneration of peripheral nervous system after injury. M2 macrophages may mediate this clearance in the same way M2 macrophages aid in the repair and regeneration in muscle and liver organs. In Drosophila plasmatocytes are responsible for disposal of all apoptotic and pathogenic microorganisms. The mechanism by which plasmatocytes recognize and engulf apoptotic debris is poorly understood, though several genes have been identified as required. We investigate similarities between signaling in mammalian M2 macrophages and plasmatocytes exposed to apoptotic corpses using genomic and in vitro systems.
Funding Provided by: Sherman Fairchild Foundation; Pomona College Neuroscience Department

Identification of Tweety family of chloride channels in rat astrocytes

Stephanie Valdez (2013); Student Collaborator(s): Christina Bejjani (2013); Mentor(s): Junryo Watanabe

Abstract: Astrocytes are uniquely positioned to play a critical role in shaping synaptic transmission between neurons as they surround glutamatergic synapses in the brain. Not only do they remove glutamate, but astrocytes also maintain ion homeostasis by removing potassium ions released by neurons as a result of electrical activity. This is critical as small changes in potassium ions can have a profound effect on the resting membrane potential of the neurons: elevated potassium levels can lead to epilepsy. One mechanism by which potassium ions are removed is via the co-removal of chloride ions via co-transporters to maintain resting membrane potential of the astrocyte. Gene expression analysis of rat astrocytes identified calcium-activated chloride channels of the Tweety family, previously described in Drosophila as having large conductance. Here we confirm the expression of TTYH1 in purified rat astrocytes using Western blotting and RT-PCR.
Funding Provided by: Sherman Fairchild Foundation; Pomona College Neuroscience Department

Abnormal Functional Connectivity of the Nucleus Accumbens in Youth with Family History of Alcoholism

Kaitlyn Casimo (2013); Student Collaborator(s): Anita Cservenka*; Additional Collaborator(s): Bonnie Nagel*; Damien Fair*; Mentor(s): Nicole Weekes
*Oregon Health and Science University

Abstract: Atypical brain response to reward is thought to be related to risk for addiction. The nucleus accumbens (NAcc) is a central aspect of the reward network and therefore might be involved in the development of alcohol use disorders (AUDs). Since a family history of alcoholism (FHP) is a strong predictor of future alcohol abuse, the goal of the current study was to compare resting state functional connectivity of the NAcc in 44 FHP youth and 42 family history negative (FHN) peers, ages 12-16. Significant group differences in functional connectivity of the NAcc were found in several areas, notably the right insula and right cerebellum. The right anterior insula showed greater segregation from the NAcc in the FHN sample and weaker segregation in the FHP group. Given that the insula is part of the cingulo-opercular network, which is important for executive functioning, the current results suggest atypically weak segregation of cognitive and reward networks in FHP youth. Interestingly, the right cerebellum showed negative functional connectivity with the NAcc in FHP youth, opposite of the positive functional connectivity between these regions that has been previously documented in adults. These results suggest atypical resting state functional connectivity between areas related to reward and cognitive control in FHP youth, which may be an indicator of future susceptibility for developing an AUD.
Funding Provided by: Claremont Colleges Neuroscience Summer Research Fellowship; NIAAA; Portland Alcohol Research Foundation; Portland Alcohol Research Foundation; Dana Foundation

An Intervention and Evaluation Method for Mental Illness Stigma

Caitlin Plefka (2013); Student Collaborator(s): Jeremy Marks (2014); Additional Collaborator(s): Roxanna Salim*; Mentor(s): Nicole Weekes
*Claremont Graduate University

Abstract: The stigma associated with mental illness is a pervasive issue that causes individuals to avoid or discontinue treatment and lose job or housing opportunities. Such stigma also contributes to lower rates of recovery. Stigma interventions seek to reverse stigmatizing attitudes and beliefs to help minimize the consequences of stigma. The success of these interventions is measured by evaluating stigmatizing attitudes and responses of participants before and after intervention. Typically, self-report inventories are used. However, such reports are vulnerable to response bias. To counteract this bias, the current study will include the implicit association task (IAT) as well as physiological measures to assess changes in stigma level following intervention. The physiological measures used will include changes in heart rate, cortisol reactivity, and galvanic skin response. In order to have the most effective intervention, we will include several strategies that have been identified as key components to reversing stigma. These include education about mental illness, contact with individuals with mental illness, and empathy building exercises aimed at understanding the experience of those with mental illness. 20 experimental (intervention +) and 20 control (intervention – ) individuals will serve as subjects. This protocol will allow us to investigate the psychological and physiological impact of a multidimensional intervention strategy on mental illness stigma.
Funding Provided by: Pomona Alumni SURP Fund (CP); Pomona College Neuroscience Department (JM)

Faces Watching Action: Investigating the Relationship Between Facial Muscle Activity and Aesthetic Judgment When Watching Dance

Arielle Snagg (2013); Additional Collaborator(s): Emily S. Cross*; Louise Kirsch*; Mentor(s): Nicole Weekes
*SoBA Laboratory; School of Psychology, Bangor University, Bangor, Wales, United Kingdom

Abstract: Studies have used dance to examine the relationship between movement perception and action. However, few studies have used dance to understand how the brain processes aesthetically pleasing experiences. We used facial EMG to investigate whether a relationship exists between aesthetic judgments of dance movements and emotions. Dance videos were presented to dance-naïve participants, who answered attentional control questions about the content of the videos in Part 1, and explicitly rated how much they liked the movements in Part 2. We predicted higher zygomaticus (“smiling” muscle) activity for movements participants liked and higher corrugator activity (“frowning” muscle) for movements they disliked. Preliminary results reveal activity in the predicted direction only for disliked movements. It is our expectation that investigating both explicit ratings and implicit patterns of facial muscle activity will help us determine whether a correlation exists between participants’ aesthetic judgments and facial responses.
Funding Provided by: Paul K. Richter and Evalyn E. Cook Richter Memorial Funds