2010 — 2011 |
Martin, Elizabeth Amanda [⬀] |
F31Activity Code Description: To provide predoctoral individuals with supervised research training in specified health and health-related areas leading toward the research degree (e.g., Ph.D.). |
Controlled Affective Processing in Anhedonia @ University of Missouri-Columbia
DESCRIPTION (provided by applicant): An objective of the Ruth L. Kirschstein NRSA is to foster the training of clinical scientists with interests that coincide with its clinical research agenda. My sponsor and I have created a research training plan consistent with this objective. My career goal is to become a successful clinical scientist at a research-intensive university conducting translational affective neuroscience research on the emotional deficits associated with treatment- refractory negative symptoms in schizophrenia. My research training plan has specific goals to help me develop the skills necessary to achieve my career goal. During this training period, my goals are to develop and increase expertise in a) schizophrenia research and methodology, b) affective neuroscience research and data analysis, c) structured and semi-structured interviewing, and d) advanced statistical techniques. I will work towards these goals while carrying out two studies, one involving people with schizophrenia and one involving healthy college students. The specific aims of my research proposal are to investigate whether anhedonia in schizophrenia is associated with poor controlled affective processing and whether controlled affective processing on an affective priming task in healthy college students is associated with medial prefrontal cortex activity. Anhedonia, or diminished experience of positive emotion for social or physical stimuli (Horan et al. 2006;Wolf, 2006) is a negative symptom of schizophrenia. Anhedonia is evident in the prodrome of schizophrenia (Hafner et al., 2003), and social anhedonia has been found to predict the onset of schizophrenia- spectrum disorders (Chapman et al., 1994;Kwapil, 1998;Gooding et al., 2005). Given that anhedonia involves decreased self-reported positive emotion, many psychopathologists have hypothesized that anhedonia might involve an emotional deficit (e.g., Berenbaum et al., 1987;Blanchard et al., 1994;Germans et al., 2000;Gooding et al., 2002). However, the exact nature of any emotional deficit in anhedonia is still unclear (Horan et al., 2006). I have found that anhedonia is associated with a controlled affective processing deficit in an at-risk population (e.g., Martin &Kerns, in press), but it is not known whether anhedonia in schizophrenia is associated with a similar deficit. In addition, to our knowledge, there has been no brain imaging research regarding the emotional functioning of people with elevated social anhedonia. However, before examining anhedonia in fMRI research, a crucial first step is to identify brain activity associated with controlled affective processing on an affective priming task, which has not been examined in previous fMRI research. This translational research will use affective neuroscience to help elucidate the emotional deficits associated with anhedonia in people with schizophrenia. In addition, this research takes an important first step towards understanding the neural correlates of anhedonia by investigating brain functioning associated with controlled affective processing in healthy controls. PUBLIC HEALTH RELEVANCE: Schizophrenia is chronic, debilitating mental illness that directly and indirectly affects the lives of millions of people. Negative symptoms in schizophrenia are especially difficult to treat and are associated with poor interpersonal and occupational functioning. Ultimately, it is hoped this program of research will aid in the prevention of schizophrenia-spectrum disorders and in the treatment of negative symptoms in schizophrenia.
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0.957 |
2020 — 2021 |
Martin, Elizabeth Anne [⬀] |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Molecular Mechanisms of Synapse Coordination
PROJECT SUMMARY / ABSTRACT The brain is an exquisitely complex organ. This complexity is not born out of its estimated 82 billion neurons, but instead in the trillions of specific connections these neurons make between one another during development called synapses. Yet, it is fundamentally unknown how the many different types of synapses form during development, nor is it known how synapse populations coordinate formation to create a working balance within in a neural circuit. This is a critical gap in the understanding of early brain development as numerous neurodevelopmental disorders, such as autism and epilepsy, are thought to arise from improper synapse formation resulting in circuit imbalances. Synapses are broadly defined into two groups: electrical synapses which form first and persist into adulthood; and chemical synapses which develop after electrical synapses and communicate via chemical neurotransmitters. While the biochemical makeup of electrical and chemical synapses are distinct, suggesting different processes regulate their formation, the autism- and epilepsy-associated gene Neurobeachin is required for both electrical and chemical synapse formation. The goal of this proposal is to 1) identify the molecular mechanisms used by Neurobeachin to regulate electrical and chemical synapse formation, and 2) determine if these mechanisms are similar to or distinct from one another. To realize this goal, the zebrafish Mauthner circuit will be used as it is ideal for dissection of Neurobeachin function during early development in vivo. Mauthner neurons make identifiable, stereotyped electrical and chemical synapses that are easily observed in developing embryos and accessible to cell biological, genetic, and biochemical investigation. Together, this proposal will unlock the shared mechanisms guiding electrical and chemical synapse formation and shed new light onto a molecule critical for brain development and implicated in various neurodevelopmental disorders ultimately leading to the design of rational therapeutic interventions. This proposal is designed to provide training in cutting edge CRISPR editing, dynamic live imaging, and sophisticated cell biology and biochemistry techniques within the zebrafish model system across early brain development at the University of Oregon. The University of Oregon is the birthplace of the zebrafish as a model organism and the preeminent institution to learn innovative zebrafish techniques among a highly collaborative and supportive environment of researchers. This experience will train the postdoctoral researcher in advanced research methodology and quantitative analysis, statistics, manuscript writing, and mentoring techniques necessary for successful growth into an independent academic research position.
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0.969 |