<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "The Role of the Medial Prefrontal Cortex in Reward Seeking: Functional Evidence on Cellular and Molecular Mechanisms underlying Drug and Natural Reward Seeking"^^ . "The medial prefrontal cortex (mPFC) is critically involved in cognitive flexibility and top down control of behavior. Dysfunction of this brain region is a hallmark of many psychiatric disorders including addiction. The physiological and molecular mechanisms underlying mPFC function are largely unclear. A widely accepted theory posits that distinct memories are encoded in the brain by sparsely distributed sets of neurons, so called neuronal ensembles,\r\nwhich has been demonstrated for reward seeking behavior. However, in the case of alcohol seeking neuronal ensembles had not been identified and it is unclear how such ensembles\r\nmight differ from those involved in natural reward seeking. Furthermore, excessive alcohol use causes damage to the mPFC, especially to its ventromedial subregion, also termed\r\ninfralimbic cortex (IL). Long-term alcohol-induced changes in this brain area include a deficit in metabotropic glutamate receptor subtype 2 (mGluR2). These receptors modify the signaling properties of IL neurons to their projection targets and their dysfunction within corticostriatal projections of alcohol-dependent rats is known to be associated with loss of control over alcohol seeking behavior. \r\nThus, this PhD thesis aims to provide insights into the organization of IL neuronal ensembles\r\ninvolved in alcohol and natural reward seeking and to further understand the role of an mGluR2 deficit for IL dependent control over alcohol seeking and cognitive flexibility.\r\n\r\nIn Study 1 we identify a functional neuronal ensemble in the IL involved in the control of\r\nalcohol seeking behavior, using a chemo-genetic inactivation method. In Study 2 we demonstrate that IL neuronal ensembles involved in alcohol and saccharin seeking are highly\r\noverlapping, but also contain reward specific components by using retrograde tracing\r\ntechniques in combination with a novel two-reward operant task. In Study 3 we develop an\r\nadvanced methodological framework for measuring neuronal ensemble activity during an\r\noperant reward seeking task using in-vivo calcium imaging. By using viral mGluR2\r\nknockdown techniques, Study 4 and 5 establish an IL mGluR2 deficit as a common\r\npathological mechanism for excessive alcohol seeking and impaired cognitive flexibility.\r\n\r\nIn summary, the results of this thesis provide important insights into the function and\r\norganization of neuronal ensembles involved in reward seeking. Possible changes of\r\norganization and function of neuronal ensembles in pathological conditions, like addiction,\r\nshould be addressed in future studies. Furthermore an IL mGluR2 deficit is established as a\r\ncommon pathological mechanism for excessive alcohol seeking and impaired cognitive\r\nflexibility, thus leading to a deeper understanding of the underlying molecular mechanisms of\r\nthis frequent comorbidity and providing a promising target for future medication therapies."^^ . "2018" . . . . . . . "Simone"^^ . "Pfarr"^^ . "Simone Pfarr"^^ . . . . . . "The Role of the Medial Prefrontal Cortex in Reward Seeking: Functional Evidence on Cellular and Molecular Mechanisms underlying Drug and Natural Reward Seeking (PDF)"^^ . . . "Dissertation_Simone_Pfarr.pdf"^^ . . . "The Role of the Medial Prefrontal Cortex in Reward Seeking: Functional Evidence on Cellular and Molecular Mechanisms underlying Drug and Natural Reward Seeking (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #25508 \n\nThe Role of the Medial Prefrontal Cortex in Reward Seeking: Functional Evidence on Cellular and Molecular Mechanisms underlying Drug and Natural Reward Seeking\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .