The animal behavioral core will support activities across the research program by conducting assessments in mouse genetic models of the 'DISC1 interactome'that will be informative about brain circuitry and psychological processes implicated in schizophrenia. The primary behavioral battery, in line with the neurodevelopmental perspective of the research program, is focused on component functions of prefrontal cortex. Paradigms developed for this purpose have revealed behavioral phenotypes clearly indicative of frontal cortical dysfunction in DISC1 transgenic mice. The use of a common behavioral platform across projects with different genetic models will provide data relevant to mechanistic hypotheses, complementing the experimental approaches used by individual investigators. The functional assessments will address behavioral flexibility, goal-directed action and the interface of action/effort with attributes of reward experience and incentive learning. Specifically, the activities of the core will 1) plan, design, and implement behavioral experiments with a focus on analytically powerful protocols targeting the prefrontal and associated forebrain systems;2) provide data analysis and interpretation of findings in support of the projects, including preparation of publications;and 3) database development for all data in the platform of behavioral assessments to allow across-project analyses and data-sharing beyond the research program.
Many clinical symptoms of schizophrenia are likely to reflect dysfunction in frontal cortical circuits. Core B will exploit behavioral assessments specifically targeting endophenotypes/phenotypes relevant to prefrontal function. Beyond its scientific value to the immediate objectives of the research program, the work will also identify assessments that are best suited to target dysfunctional mechanisms in animal models of schizophrenia.
|Li, Ye; Viscidi, Raphael P; Kannan, Geetha et al. (2018) Chronic Toxoplasma gondii Infection Induces Anti-N-Methyl-d-Aspartate Receptor Autoantibodies and Associated Behavioral Changes and Neuropathology. Infect Immun 86:|
|Lindgren, Maija; Torniainen-Holm, Minna; Härkänen, Tommi et al. (2018) The association between toxoplasma and the psychosis continuum in a general population setting. Schizophr Res 193:329-335|
|Sedlak, Thomas W; Nucifora, Leslie G; Koga, Minori et al. (2018) Sulforaphane Augments Glutathione and Influences Brain Metabolites in Human Subjects: A Clinical Pilot Study. Mol Neuropsychiatry 3:214-222|
|McFarland, Ross; Wang, Zi Teng; Jouroukhin, Yan et al. (2018) AAH2 gene is not required for dopamine-dependent neurochemical and behavioral abnormalities produced by Toxoplasma infection in mouse. Behav Brain Res 347:193-200|
|Severance, Emily G; Yolken, Robert H (2018) Deciphering microbiome and neuroactive immune gene interactions in schizophrenia. Neurobiol Dis :|
|Sumitomo, Akiko; Yukitake, Hiroshi; Hirai, Kazuko et al. (2018) Ulk2 controls cortical excitatory-inhibitory balance via autophagic regulation of p62 and GABAA receptor trafficking in pyramidal neurons. Hum Mol Genet 27:3165-3176|
|Endo, Ryo; Takashima, Noriko; Nekooki-Machida, Yoko et al. (2018) TAR DNA-Binding Protein 43 and Disrupted in Schizophrenia 1 Coaggregation Disrupts Dendritic Local Translation and Mental Function in Frontotemporal Lobar Degeneration. Biol Psychiatry 84:509-521|
|Koh, Ming Teng; Ahrens, Paige S; Gallagher, Michela (2018) A greater tendency for representation mediated learning in a ketamine mouse model of schizophrenia. Behav Neurosci 132:106-113|
|Gusev, Alexander; Mancuso, Nicholas; Won, Hyejung et al. (2018) Transcriptome-wide association study of schizophrenia and chromatin activity yields mechanistic disease insights. Nat Genet 50:538-548|
|Koh, Ming Teng; Shao, Yi; Rosenzweig-Lipson, Sharon et al. (2018) Treatment with levetiracetam improves cognition in a ketamine rat model of schizophrenia. Schizophr Res 193:119-125|
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