ingest cdrApp 2018-06-13T21:27:29.935Z 51cd2fe2-3fd7-401f-a923-a97bc3db68a2 modifyDatastreamByValue RELS-EXT fedoraAdmin 2018-06-13T23:01:03.842Z Setting exclusive relation addDatastream MD_TECHNICAL fedoraAdmin 2018-06-13T23:01:15.079Z Adding technical metadata derived by FITS addDatastream MD_FULL_TEXT fedoraAdmin 2018-06-13T23:01:38.190Z Adding full text metadata extracted by Apache Tika modifyDatastreamByValue RELS-EXT fedoraAdmin 2018-06-13T23:02:00.216Z Setting exclusive relation modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-07-10T20:25:49.999Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-07-17T16:41:08.359Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-08-02T16:44:21.416Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-08-08T16:07:28.775Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-08-14T20:31:01.579Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-08-16T16:16:49.172Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-09-21T13:52:00.116Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-09-26T16:44:10.323Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-10-10T17:05:58.411Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-10-11T17:38:22.995Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2019-02-28T00:37:25.484Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2019-03-19T19:54:37.972Z Sarah Schoenrock Author Neuroscience Curriculum School of Medicine USING THE COLLABORATIVE CROSS MOUSE POPULATION TO INVESTIGATE ENVIRONMENTAL AND GENETIC FACTORS THAT INFLUENCE COMPLEX BEHAVIORS Affective disorders and substance abuse disorders (SUDs) are highly prevalent within the US and result in substantial burdens on the affected individual, their loved ones, and society. Relatively few effective treatments exist however, due to a lack of understanding regarding the etiology of these complex disorders. Development of affective and SUDs are due to both environmental factors, (i.e. perinatal insults, childhood maltreatment, stressful life events), genetic background and the complex interplay of the two. Using inbred strains of mice can potentially disentangle the two (environment and genetic factors), and elucidate their interactions to aid in the identification of specific mechanisms. However, traditional inbred strains pose some limitations in the variation of genetic diversity present, which limits our ability to capture a full phenotypic range that may better model disease states seen in humans. In this thesis, we use a relatively new population of recombinant inbred strains, the Collaborative Cross (CC), that were designed to have increased genetic, and therefore phenotypic, diversity over traditional inbred strains. We used a panel of female F1 hybrids of CC strains (RIX) to investigate the effects of an environmental factor, nutritional deficiency in the perinatal period, genetic background, parent-of-origin (PO) and any interactions on stress response, anxiety-, and depressive-like behaviors inadulthood. From this phenotypic screen, we identified two RIX lines (RIX 41/51 and 04/17) that were outliers for novelty-induced locomotion, a predictive trait for addiction-related behaviors. We characterized RIX 41/51 and 04/17 for cocaine (COC)-related behaviors and possible underlying mechanisms including COC metabolism, HPA axis dysregulation and dopamine dynamics in the striatum. We also performed QTL mapping for low initial locomotor response to COC using an F2 intercross of CC041/TauUnc and C57BL/6NJ and identified three significant QTLs on Chr 7, 11 and 14. These studies are the first to assess the CC or RIX of CC for addiction-related behaviors and provides evidence that RIX 41/51 and 04/17 are novel models with a unique genetic diversity to study the underlying mechanisms involved in COC-related behaviors. Spring 2018 2018 Neurosciences Genetics Behavioral sciences eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Neurobiology Lisa Tarantino Thesis advisor Thomas Kash Thesis advisor Joyce Besheer Thesis advisor Leslie Morrow Thesis advisor William Valdar Thesis advisor Fernando Pardo Manuel de Villena Thesis advisor Lisa Tarantino Thesis advisor text Sarah Schoenrock Author Neuroscience Curriculum School of Medicine USING THE COLLABORATIVE CROSS MOUSE POPULATION TO INVESTIGATE ENVIRONMENTAL AND GENETIC FACTORS THAT INFLUENCE COMPLEX BEHAVIORS Affective disorders and substance abuse disorders (SUDs) are highly prevalent within the US and result in substantial burdens on the affected individual, their loved ones, and society. Relatively few effective treatments exist however, due to a lack of understanding regarding the etiology of these complex disorders. Development of affective and SUDs are due to both environmental factors, (i.e. perinatal insults, childhood maltreatment, stressful life events), genetic background and the complex interplay of the two. Using inbred strains of mice can potentially disentangle the two (environment and genetic factors), and elucidate their interactions to aid in the identification of specific mechanisms. However, traditional inbred strains pose some limitations in the variation of genetic diversity present, which limits our ability to capture a full phenotypic range that may better model disease states seen in humans. In this thesis, we use a relatively new population of recombinant inbred strains, the Collaborative Cross (CC), that were designed to have increased genetic, and therefore phenotypic, diversity over traditional inbred strains. We used a panel of female F1 hybrids of CC strains (RIX) to investigate the effects of an environmental factor, nutritional deficiency in the perinatal period, genetic background, parent-of-origin (PO) and any interactions on stress response, anxiety-, and depressive-like behaviors inadulthood. From this phenotypic screen, we identified two RIX lines (RIX 41/51 and 04/17) that were outliers for novelty-induced locomotion, a predictive trait for addiction-related behaviors. We characterized RIX 41/51 and 04/17 for cocaine (COC)-related behaviors and possible underlying mechanisms including COC metabolism, HPA axis dysregulation and dopamine dynamics in the striatum. We also performed QTL mapping for low initial locomotor response to COC using an F2 intercross of CC041/TauUnc and C57BL/6NJ and identified three significant QTLs on Chr 7, 11 and 14. These studies are the first to assess the CC or RIX of CC for addiction-related behaviors and provides evidence that RIX 41/51 and 04/17 are novel models with a unique genetic diversity to study the underlying mechanisms involved in COC-related behaviors. Spring 2018 2018 Neurosciences Genetics Behavioral sciences eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Neurobiology Lisa Tarantino Thesis advisor Thomas Kash Thesis advisor Joyce Besheer Thesis advisor Leslie Morrow Thesis advisor William Valdar Thesis advisor Fernando Pardo Manuel de Villena Thesis advisor Lisa Tarantino Thesis advisor text Sarah Schoenrock Author Neuroscience Curriculum School of Medicine USING THE COLLABORATIVE CROSS MOUSE POPULATION TO INVESTIGATE ENVIRONMENTAL AND GENETIC FACTORS THAT INFLUENCE COMPLEX BEHAVIORS Affective disorders and substance abuse disorders (SUDs) are highly prevalent within the US and result in substantial burdens on the affected individual, their loved ones, and society. Relatively few effective treatments exist however, due to a lack of understanding regarding the etiology of these complex disorders. Development of affective and SUDs are due to both environmental factors, (i.e. perinatal insults, childhood maltreatment, stressful life events), genetic background and the complex interplay of the two. Using inbred strains of mice can potentially disentangle the two (environment and genetic factors), and elucidate their interactions to aid in the identification of specific mechanisms. However, traditional inbred strains pose some limitations in the variation of genetic diversity present, which limits our ability to capture a full phenotypic range that may better model disease states seen in humans. In this thesis, we use a relatively new population of recombinant inbred strains, the Collaborative Cross (CC), that were designed to have increased genetic, and therefore phenotypic, diversity over traditional inbred strains. We used a panel of female F1 hybrids of CC strains (RIX) to investigate the effects of an environmental factor, nutritional deficiency in the perinatal period, genetic background, parent-of-origin (PO) and any interactions on stress response, anxiety-, and depressive-like behaviors inadulthood. From this phenotypic screen, we identified two RIX lines (RIX 41/51 and 04/17) that were outliers for novelty-induced locomotion, a predictive trait for addiction-related behaviors. We characterized RIX 41/51 and 04/17 for cocaine (COC)-related behaviors and possible underlying mechanisms including COC metabolism, HPA axis dysregulation and dopamine dynamics in the striatum. We also performed QTL mapping for low initial locomotor response to COC using an F2 intercross of CC041/TauUnc and C57BL/6NJ and identified three significant QTLs on Chr 7, 11 and 14. These studies are the first to assess the CC or RIX of CC for addiction-related behaviors and provides evidence that RIX 41/51 and 04/17 are novel models with a unique genetic diversity to study the underlying mechanisms involved in COC-related behaviors. Spring 2018 2018 Neurosciences Genetics Behavioral sciences eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Neurobiology Lisa Tarantino Thesis advisor Thomas Kash Thesis advisor Joyce Besheer Thesis advisor Leslie Morrow Thesis advisor William Valdar Thesis advisor Fernando Pardo Manuel de Villena Thesis advisor Lisa Tarantino Thesis advisor text Sarah Schoenrock Author Neuroscience Curriculum School of Medicine USING THE COLLABORATIVE CROSS MOUSE POPULATION TO INVESTIGATE ENVIRONMENTAL AND GENETIC FACTORS THAT INFLUENCE COMPLEX BEHAVIORS Affective disorders and substance abuse disorders (SUDs) are highly prevalent within the US and result in substantial burdens on the affected individual, their loved ones, and society. Relatively few effective treatments exist however, due to a lack of understanding regarding the etiology of these complex disorders. Development of affective and SUDs are due to both environmental factors, (i.e. perinatal insults, childhood maltreatment, stressful life events), genetic background and the complex interplay of the two. Using inbred strains of mice can potentially disentangle the two (environment and genetic factors), and elucidate their interactions to aid in the identification of specific mechanisms. However, traditional inbred strains pose some limitations in the variation of genetic diversity present, which limits our ability to capture a full phenotypic range that may better model disease states seen in humans. In this thesis, we use a relatively new population of recombinant inbred strains, the Collaborative Cross (CC), that were designed to have increased genetic, and therefore phenotypic, diversity over traditional inbred strains. We used a panel of female F1 hybrids of CC strains (RIX) to investigate the effects of an environmental factor, nutritional deficiency in the perinatal period, genetic background, parent-of-origin (PO) and any interactions on stress response, anxiety-, and depressive-like behaviors inadulthood. From this phenotypic screen, we identified two RIX lines (RIX 41/51 and 04/17) that were outliers for novelty-induced locomotion, a predictive trait for addiction-related behaviors. We characterized RIX 41/51 and 04/17 for cocaine (COC)-related behaviors and possible underlying mechanisms including COC metabolism, HPA axis dysregulation and dopamine dynamics in the striatum. We also performed QTL mapping for low initial locomotor response to COC using an F2 intercross of CC041/TauUnc and C57BL/6NJ and identified three significant QTLs on Chr 7, 11 and 14. These studies are the first to assess the CC or RIX of CC for addiction-related behaviors and provides evidence that RIX 41/51 and 04/17 are novel models with a unique genetic diversity to study the underlying mechanisms involved in COC-related behaviors. Spring 2018 2018 Neurosciences Genetics Behavioral sciences eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Neurobiology Lisa Tarantino Thesis advisor Thomas Kash Thesis advisor Joyce Besheer Thesis advisor A. Leslie Morrow Thesis advisor William Valdar Thesis advisor Fernando Pardo Manuel Pardo-Pardo-Manuel de Villena Thesis advisor Lisa Tarantino Thesis advisor text Sarah Schoenrock Author Neuroscience Curriculum School of Medicine USING THE COLLABORATIVE CROSS MOUSE POPULATION TO INVESTIGATE ENVIRONMENTAL AND GENETIC FACTORS THAT INFLUENCE COMPLEX BEHAVIORS Affective disorders and substance abuse disorders (SUDs) are highly prevalent within the US and result in substantial burdens on the affected individual, their loved ones, and society. Relatively few effective treatments exist however, due to a lack of understanding regarding the etiology of these complex disorders. Development of affective and SUDs are due to both environmental factors, (i.e. perinatal insults, childhood maltreatment, stressful life events), genetic background and the complex interplay of the two. Using inbred strains of mice can potentially disentangle the two (environment and genetic factors), and elucidate their interactions to aid in the identification of specific mechanisms. However, traditional inbred strains pose some limitations in the variation of genetic diversity present, which limits our ability to capture a full phenotypic range that may better model disease states seen in humans. In this thesis, we use a relatively new population of recombinant inbred strains, the Collaborative Cross (CC), that were designed to have increased genetic, and therefore phenotypic, diversity over traditional inbred strains. We used a panel of female F1 hybrids of CC strains (RIX) to investigate the effects of an environmental factor, nutritional deficiency in the perinatal period, genetic background, parent-of-origin (PO) and any interactions on stress response, anxiety-, and depressive-like behaviors inadulthood. From this phenotypic screen, we identified two RIX lines (RIX 41/51 and 04/17) that were outliers for novelty-induced locomotion, a predictive trait for addiction-related behaviors. We characterized RIX 41/51 and 04/17 for cocaine (COC)-related behaviors and possible underlying mechanisms including COC metabolism, HPA axis dysregulation and dopamine dynamics in the striatum. We also performed QTL mapping for low initial locomotor response to COC using an F2 intercross of CC041/TauUnc and C57BL/6NJ and identified three significant QTLs on Chr 7, 11 and 14. These studies are the first to assess the CC or RIX of CC for addiction-related behaviors and provides evidence that RIX 41/51 and 04/17 are novel models with a unique genetic diversity to study the underlying mechanisms involved in COC-related behaviors. Spring 2018 2018 Neurosciences Genetics Behavioral sciences eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Neurobiology Lisa Tarantino Thesis advisor Thomas Kash Thesis advisor Joyce Besheer Thesis advisor A. Leslie Morrow Thesis advisor William Valdar Thesis advisor Fernando Pardo Manuel Pardo-Pardo-Manuel de Villena Thesis advisor Lisa Tarantino Thesis advisor text Sarah Schoenrock Author Neuroscience Curriculum School of Medicine USING THE COLLABORATIVE CROSS MOUSE POPULATION TO INVESTIGATE ENVIRONMENTAL AND GENETIC FACTORS THAT INFLUENCE COMPLEX BEHAVIORS Affective disorders and substance abuse disorders (SUDs) are highly prevalent within the US and result in substantial burdens on the affected individual, their loved ones, and society. Relatively few effective treatments exist however, due to a lack of understanding regarding the etiology of these complex disorders. Development of affective and SUDs are due to both environmental factors, (i.e. perinatal insults, childhood maltreatment, stressful life events), genetic background and the complex interplay of the two. Using inbred strains of mice can potentially disentangle the two (environment and genetic factors), and elucidate their interactions to aid in the identification of specific mechanisms. However, traditional inbred strains pose some limitations in the variation of genetic diversity present, which limits our ability to capture a full phenotypic range that may better model disease states seen in humans. In this thesis, we use a relatively new population of recombinant inbred strains, the Collaborative Cross (CC), that were designed to have increased genetic, and therefore phenotypic, diversity over traditional inbred strains. We used a panel of female F1 hybrids of CC strains (RIX) to investigate the effects of an environmental factor, nutritional deficiency in the perinatal period, genetic background, parent-of-origin (PO) and any interactions on stress response, anxiety-, and depressive-like behaviors inadulthood. From this phenotypic screen, we identified two RIX lines (RIX 41/51 and 04/17) that were outliers for novelty-induced locomotion, a predictive trait for addiction-related behaviors. We characterized RIX 41/51 and 04/17 for cocaine (COC)-related behaviors and possible underlying mechanisms including COC metabolism, HPA axis dysregulation and dopamine dynamics in the striatum. We also performed QTL mapping for low initial locomotor response to COC using an F2 intercross of CC041/TauUnc and C57BL/6NJ and identified three significant QTLs on Chr 7, 11 and 14. These studies are the first to assess the CC or RIX of CC for addiction-related behaviors and provides evidence that RIX 41/51 and 04/17 are novel models with a unique genetic diversity to study the underlying mechanisms involved in COC-related behaviors. Spring 2018 2018 Neurosciences Genetics Behavioral sciences eng Doctor of Philosophy Dissertation Neurobiology Lisa Tarantino Thesis advisor Thomas Kash Thesis advisor Joyce Besheer Thesis advisor A. Leslie Morrow Thesis advisor William Valdar Thesis advisor Fernando Pardo Manuel Pardo-Pardo-Manuel de Villena Thesis advisor Lisa Tarantino Thesis advisor text University of North Carolina at Chapel Hill Degree granting institution Sarah Schoenrock Author Neuroscience Curriculum School of Medicine USING THE COLLABORATIVE CROSS MOUSE POPULATION TO INVESTIGATE ENVIRONMENTAL AND GENETIC FACTORS THAT INFLUENCE COMPLEX BEHAVIORS Affective disorders and substance abuse disorders (SUDs) are highly prevalent within the US and result in substantial burdens on the affected individual, their loved ones, and society. Relatively few effective treatments exist however, due to a lack of understanding regarding the etiology of these complex disorders. Development of affective and SUDs are due to both environmental factors, (i.e. perinatal insults, childhood maltreatment, stressful life events), genetic background and the complex interplay of the two. Using inbred strains of mice can potentially disentangle the two (environment and genetic factors), and elucidate their interactions to aid in the identification of specific mechanisms. However, traditional inbred strains pose some limitations in the variation of genetic diversity present, which limits our ability to capture a full phenotypic range that may better model disease states seen in humans. In this thesis, we use a relatively new population of recombinant inbred strains, the Collaborative Cross (CC), that were designed to have increased genetic, and therefore phenotypic, diversity over traditional inbred strains. We used a panel of female F1 hybrids of CC strains (RIX) to investigate the effects of an environmental factor, nutritional deficiency in the perinatal period, genetic background, parent-of-origin (PO) and any interactions on stress response, anxiety-, and depressive-like behaviors inadulthood. From this phenotypic screen, we identified two RIX lines (RIX 41/51 and 04/17) that were outliers for novelty-induced locomotion, a predictive trait for addiction-related behaviors. We characterized RIX 41/51 and 04/17 for cocaine (COC)-related behaviors and possible underlying mechanisms including COC metabolism, HPA axis dysregulation and dopamine dynamics in the striatum. We also performed QTL mapping for low initial locomotor response to COC using an F2 intercross of CC041/TauUnc and C57BL/6NJ and identified three significant QTLs on Chr 7, 11 and 14. These studies are the first to assess the CC or RIX of CC for addiction-related behaviors and provides evidence that RIX 41/51 and 04/17 are novel models with a unique genetic diversity to study the underlying mechanisms involved in COC-related behaviors. Spring 2018 2018 Neurosciences Genetics Behavioral sciences eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Neurobiology Lisa Tarantino Thesis advisor Thomas Kash Thesis advisor Joyce Besheer Thesis advisor Leslie Morrow Thesis advisor William Valdar Thesis advisor Fernando Pardo Manuel de Villena Thesis advisor Lisa Tarantino Thesis advisor text Sarah Schoenrock Author Neuroscience Curriculum School of Medicine USING THE COLLABORATIVE CROSS MOUSE POPULATION TO INVESTIGATE ENVIRONMENTAL AND GENETIC FACTORS THAT INFLUENCE COMPLEX BEHAVIORS Affective disorders and substance abuse disorders (SUDs) are highly prevalent within the US and result in substantial burdens on the affected individual, their loved ones, and society. Relatively few effective treatments exist however, due to a lack of understanding regarding the etiology of these complex disorders. Development of affective and SUDs are due to both environmental factors, (i.e. perinatal insults, childhood maltreatment, stressful life events), genetic background and the complex interplay of the two. Using inbred strains of mice can potentially disentangle the two (environment and genetic factors), and elucidate their interactions to aid in the identification of specific mechanisms. However, traditional inbred strains pose some limitations in the variation of genetic diversity present, which limits our ability to capture a full phenotypic range that may better model disease states seen in humans. In this thesis, we use a relatively new population of recombinant inbred strains, the Collaborative Cross (CC), that were designed to have increased genetic, and therefore phenotypic, diversity over traditional inbred strains. We used a panel of female F1 hybrids of CC strains (RIX) to investigate the effects of an environmental factor, nutritional deficiency in the perinatal period, genetic background, parent-of-origin (PO) and any interactions on stress response, anxiety-, and depressive-like behaviors inadulthood. From this phenotypic screen, we identified two RIX lines (RIX 41/51 and 04/17) that were outliers for novelty-induced locomotion, a predictive trait for addiction-related behaviors. We characterized RIX 41/51 and 04/17 for cocaine (COC)-related behaviors and possible underlying mechanisms including COC metabolism, HPA axis dysregulation and dopamine dynamics in the striatum. We also performed QTL mapping for low initial locomotor response to COC using an F2 intercross of CC041/TauUnc and C57BL/6NJ and identified three significant QTLs on Chr 7, 11 and 14. These studies are the first to assess the CC or RIX of CC for addiction-related behaviors and provides evidence that RIX 41/51 and 04/17 are novel models with a unique genetic diversity to study the underlying mechanisms involved in COC-related behaviors. Spring 2018 2018 Neurosciences Genetics Behavioral sciences eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Neurobiology Lisa Tarantino Thesis advisor Thomas Kash Thesis advisor Joyce Besheer Thesis advisor Leslie Morrow Thesis advisor William Valdar Thesis advisor Fernando Pardo Manuel de Villena Thesis advisor Lisa Tarantino Thesis advisor text Sarah Schoenrock Creator Neuroscience Curriculum School of Medicine USING THE COLLABORATIVE CROSS MOUSE POPULATION TO INVESTIGATE ENVIRONMENTAL AND GENETIC FACTORS THAT INFLUENCE COMPLEX BEHAVIORS Affective disorders and substance abuse disorders (SUDs) are highly prevalent within the US and result in substantial burdens on the affected individual, their loved ones, and society. Relatively few effective treatments exist however, due to a lack of understanding regarding the etiology of these complex disorders. Development of affective and SUDs are due to both environmental factors, (i.e. perinatal insults, childhood maltreatment, stressful life events), genetic background and the complex interplay of the two. Using inbred strains of mice can potentially disentangle the two (environment and genetic factors), and elucidate their interactions to aid in the identification of specific mechanisms. However, traditional inbred strains pose some limitations in the variation of genetic diversity present, which limits our ability to capture a full phenotypic range that may better model disease states seen in humans. In this thesis, we use a relatively new population of recombinant inbred strains, the Collaborative Cross (CC), that were designed to have increased genetic, and therefore phenotypic, diversity over traditional inbred strains. We used a panel of female F1 hybrids of CC strains (RIX) to investigate the effects of an environmental factor, nutritional deficiency in the perinatal period, genetic background, parent-of-origin (PO) and any interactions on stress response, anxiety-, and depressive-like behaviors inadulthood. From this phenotypic screen, we identified two RIX lines (RIX 41/51 and 04/17) that were outliers for novelty-induced locomotion, a predictive trait for addiction-related behaviors. We characterized RIX 41/51 and 04/17 for cocaine (COC)-related behaviors and possible underlying mechanisms including COC metabolism, HPA axis dysregulation and dopamine dynamics in the striatum. We also performed QTL mapping for low initial locomotor response to COC using an F2 intercross of CC041/TauUnc and C57BL/6NJ and identified three significant QTLs on Chr 7, 11 and 14. These studies are the first to assess the CC or RIX of CC for addiction-related behaviors and provides evidence that RIX 41/51 and 04/17 are novel models with a unique genetic diversity to study the underlying mechanisms involved in COC-related behaviors. Neurosciences Genetics Behavioral sciences eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Neurobiology Lisa Tarantino Thesis advisor Thomas Kash Thesis advisor Joyce Besheer Thesis advisor Leslie Morrow Thesis advisor William Valdar Thesis advisor Fernando Pardo Manuel de Villena Thesis advisor Lisa Tarantino Thesis advisor text 2018 2018-05 Sarah Schoenrock Author Neuroscience Curriculum School of Medicine USING THE COLLABORATIVE CROSS MOUSE POPULATION TO INVESTIGATE ENVIRONMENTAL AND GENETIC FACTORS THAT INFLUENCE COMPLEX BEHAVIORS Affective disorders and substance abuse disorders (SUDs) are highly prevalent within the US and result in substantial burdens on the affected individual, their loved ones, and society. Relatively few effective treatments exist however, due to a lack of understanding regarding the etiology of these complex disorders. Development of affective and SUDs are due to both environmental factors, (i.e. perinatal insults, childhood maltreatment, stressful life events), genetic background and the complex interplay of the two. Using inbred strains of mice can potentially disentangle the two (environment and genetic factors), and elucidate their interactions to aid in the identification of specific mechanisms. However, traditional inbred strains pose some limitations in the variation of genetic diversity present, which limits our ability to capture a full phenotypic range that may better model disease states seen in humans. In this thesis, we use a relatively new population of recombinant inbred strains, the Collaborative Cross (CC), that were designed to have increased genetic, and therefore phenotypic, diversity over traditional inbred strains. We used a panel of female F1 hybrids of CC strains (RIX) to investigate the effects of an environmental factor, nutritional deficiency in the perinatal period, genetic background, parent-of-origin (PO) and any interactions on stress response, anxiety-, and depressive-like behaviors inadulthood. From this phenotypic screen, we identified two RIX lines (RIX 41/51 and 04/17) that were outliers for novelty-induced locomotion, a predictive trait for addiction-related behaviors. We characterized RIX 41/51 and 04/17 for cocaine (COC)-related behaviors and possible underlying mechanisms including COC metabolism, HPA axis dysregulation and dopamine dynamics in the striatum. We also performed QTL mapping for low initial locomotor response to COC using an F2 intercross of CC041/TauUnc and C57BL/6NJ and identified three significant QTLs on Chr 7, 11 and 14. These studies are the first to assess the CC or RIX of CC for addiction-related behaviors and provides evidence that RIX 41/51 and 04/17 are novel models with a unique genetic diversity to study the underlying mechanisms involved in COC-related behaviors. Spring 2018 2018 Neurosciences Genetics Behavioral sciences eng Doctor of Philosophy Dissertation Neurobiology Lisa Tarantino Thesis advisor Thomas Kash Thesis advisor Joyce Besheer Thesis advisor A. Leslie Morrow Thesis advisor William Valdar Thesis advisor Fernando Pardo Manuel Pardo-Pardo-Manuel de Villena Thesis advisor Lisa Tarantino Thesis advisor text University of North Carolina at Chapel Hill Degree granting institution Sarah Schoenrock Author Neuroscience Curriculum School of Medicine USING THE COLLABORATIVE CROSS MOUSE POPULATION TO INVESTIGATE ENVIRONMENTAL AND GENETIC FACTORS THAT INFLUENCE COMPLEX BEHAVIORS Affective disorders and substance abuse disorders (SUDs) are highly prevalent within the US and result in substantial burdens on the affected individual, their loved ones, and society. Relatively few effective treatments exist however, due to a lack of understanding regarding the etiology of these complex disorders. Development of affective and SUDs are due to both environmental factors, (i.e. perinatal insults, childhood maltreatment, stressful life events), genetic background and the complex interplay of the two. Using inbred strains of mice can potentially disentangle the two (environment and genetic factors), and elucidate their interactions to aid in the identification of specific mechanisms. However, traditional inbred strains pose some limitations in the variation of genetic diversity present, which limits our ability to capture a full phenotypic range that may better model disease states seen in humans. In this thesis, we use a relatively new population of recombinant inbred strains, the Collaborative Cross (CC), that were designed to have increased genetic, and therefore phenotypic, diversity over traditional inbred strains. We used a panel of female F1 hybrids of CC strains (RIX) to investigate the effects of an environmental factor, nutritional deficiency in the perinatal period, genetic background, parent-of-origin (PO) and any interactions on stress response, anxiety-, and depressive-like behaviors inadulthood. From this phenotypic screen, we identified two RIX lines (RIX 41/51 and 04/17) that were outliers for novelty-induced locomotion, a predictive trait for addiction-related behaviors. We characterized RIX 41/51 and 04/17 for cocaine (COC)-related behaviors and possible underlying mechanisms including COC metabolism, HPA axis dysregulation and dopamine dynamics in the striatum. We also performed QTL mapping for low initial locomotor response to COC using an F2 intercross of CC041/TauUnc and C57BL/6NJ and identified three significant QTLs on Chr 7, 11 and 14. These studies are the first to assess the CC or RIX of CC for addiction-related behaviors and provides evidence that RIX 41/51 and 04/17 are novel models with a unique genetic diversity to study the underlying mechanisms involved in COC-related behaviors. Spring 2018 2018 Neurosciences Genetics Behavioral sciences eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Neurobiology Lisa Tarantino Thesis advisor Thomas Kash Thesis advisor Joyce Besheer Thesis advisor A. Leslie Morrow Thesis advisor William Valdar Thesis advisor Fernando Pardo Manuel Pardo-Pardo-Manuel de Villena Thesis advisor Lisa Tarantino Thesis advisor text Sarah Schoenrock Creator Neuroscience Curriculum School of Medicine Affective disorders and substance abuse disorders (SUDs) are highly prevalent within the US and result in substantial burdens on the affected individual, their loved ones, and society. Relatively few effective treatments exist however, due to a lack of understanding regarding the etiology of these complex disorders. Development of affective and SUDs are due to both environmental factors, (i.e. perinatal insults, childhood maltreatment, stressful life events), genetic background and the complex interplay of the two. Using inbred strains of mice can potentially disentangle the two (environment and genetic factors), and elucidate their interactions to aid in the identification of specific mechanisms. However, traditional inbred strains pose some limitations in the variation of genetic diversity present, which limits our ability to capture a full phenotypic range that may better model disease states seen in humans. In this thesis, we use a relatively new population of recombinant inbred strains, the Collaborative Cross (CC), that were designed to have increased genetic, and therefore phenotypic, diversity over traditional inbred strains. We used a panel of female F1 hybrids of CC strains (RIX) to investigate the effects of an environmental factor, nutritional deficiency in the perinatal period, genetic background, parent-of-origin (PO) and any interactions on stress response, anxiety-, and depressive-like behaviors inadulthood. From this phenotypic screen, we identified two RIX lines (RIX 41/51 and 04/17) that were outliers for novelty-induced locomotion, a predictive trait for addiction-related behaviors. We characterized RIX 41/51 and 04/17 for cocaine (COC)-related behaviors and possible underlying mechanisms including COC metabolism, HPA axis dysregulation and dopamine dynamics in the striatum. We also performed QTL mapping for low initial locomotor response to COC using an F2 intercross of CC041/TauUnc and C57BL/6NJ and identified three significant QTLs on Chr 7, 11 and 14. These studies are the first to assess the CC or RIX of CC for addiction-related behaviors and provides evidence that RIX 41/51 and 04/17 are novel models with a unique genetic diversity to study the underlying mechanisms involved in COC-related behaviors. 2018-05 2018 Neurosciences Genetics Behavioral sciences eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Neurobiology Lisa Tarantino Thesis advisor Thomas Kash Thesis advisor Joyce Besheer Thesis advisor A. Leslie Morrow Thesis advisor William Valdar Thesis advisor Fernando Pardo Manuel Pardo-Pardo-Manuel de Villena Thesis advisor Lisa Tarantino Thesis advisor text Sarah Schoenrock Creator Neuroscience Curriculum School of Medicine Affective disorders and substance abuse disorders (SUDs) are highly prevalent within the US and result in substantial burdens on the affected individual, their loved ones, and society. Relatively few effective treatments exist however, due to a lack of understanding regarding the etiology of these complex disorders. Development of affective and SUDs are due to both environmental factors, (i.e. perinatal insults, childhood maltreatment, stressful life events), genetic background and the complex interplay of the two. Using inbred strains of mice can potentially disentangle the two (environment and genetic factors), and elucidate their interactions to aid in the identification of specific mechanisms. However, traditional inbred strains pose some limitations in the variation of genetic diversity present, which limits our ability to capture a full phenotypic range that may better model disease states seen in humans. In this thesis, we use a relatively new population of recombinant inbred strains, the Collaborative Cross (CC), that were designed to have increased genetic, and therefore phenotypic, diversity over traditional inbred strains. We used a panel of female F1 hybrids of CC strains (RIX) to investigate the effects of an environmental factor, nutritional deficiency in the perinatal period, genetic background, parent-of-origin (PO) and any interactions on stress response, anxiety-, and depressive-like behaviors inadulthood. From this phenotypic screen, we identified two RIX lines (RIX 41/51 and 04/17) that were outliers for novelty-induced locomotion, a predictive trait for addiction-related behaviors. We characterized RIX 41/51 and 04/17 for cocaine (COC)-related behaviors and possible underlying mechanisms including COC metabolism, HPA axis dysregulation and dopamine dynamics in the striatum. We also performed QTL mapping for low initial locomotor response to COC using an F2 intercross of CC041/TauUnc and C57BL/6NJ and identified three significant QTLs on Chr 7, 11 and 14. These studies are the first to assess the CC or RIX of CC for addiction-related behaviors and provides evidence that RIX 41/51 and 04/17 are novel models with a unique genetic diversity to study the underlying mechanisms involved in COC-related behaviors. 2018-05 2018 Neurosciences Genetics Behavioral sciences eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Lisa Tarantino Thesis advisor Thomas Kash Thesis advisor Joyce Besheer Thesis advisor A. Leslie Morrow Thesis advisor William Valdar Thesis advisor Fernando Pardo Manuel Pardo-Pardo-Manuel de Villena Thesis advisor Lisa Tarantino Thesis advisor text Schoenrock_unc_0153D_17514.pdf uuid:a0e9b5a4-4c85-4110-a57b-f72467d4fe46 2020-06-13T00:00:00 2018-02-08T14:29:02Z proquest application/pdf 10631539