Koch, Michael
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Item-typ:Veröffentlichung, Investigation of neuronal structures and networks on the modulation of decision-making and impulse control by temporary inactivation via local microinfusion of the GABAA receptor agonist muscimol in rats(2014-09-17); ; ; Impulsivity is determined by deficits in decision-making (impulsive choice) and impulse control (impulsive action). Using reversible inactivation via microinfusion of the GABAA receptor agonist muscimol the thesis aimed to elucidate the participation of the ventral medial prefrontal cortex (vmPFC), the nucleus accumbens (NAc) core and shell as well as the connections of the vmPFC and the NAc subregions in both forms of impulsivity in rats. The present results indicate that impulse control is regulated by both structures, while impulsive decision-making is principally modulated by the NAc, and not the vmPFC. The current investigation suggests both functional dissociations and close interactions between the vmPFC and NAc in terms of impulsive action, depending on the involved accumbal subregion. The NAc shell constitutes the critical region mediating both types of impulsivity, whereas the NAc core seems to be implicated in non-specific impairments beyond impulsive choice. Consequently, this work points towards various specific frontostriatal systems differentially contributing to delay-based decision-making and particularly impulse control.Dissertation372 220 - Some of the metrics are blocked by yourconsent settings
Item-typ:Veröffentlichung, Adult neurogenesis as a potential source for regeneration of structural brain damage : Redirection of neuronal precursor cells from the rostral migratory stream into prefrontal cortex lesions in adult rats(2018-12-18); ; ; Up until today physical brain damage is incurable. Whenever cells of the central nervous system are lost, either due to a traumatic brain injury, stroke, or neurodegenerative diseases, they are considered irretrievably lost. Nonetheless, the adult mammalian brain features two distinct areas capable of continuous production of neuronal precursor cells: The subgranular zone of the hippocampus and the subventricular zone around the walls of the lateral ventricles. The subventricular zone-derived neuroblasts follow a rigid migratory path, the rostral migratory stream (RMS), through the forebrain towards the olfactory bulb. En route they form elongated aggregates, so called migration chains, which accelerate the migration, but also hinder the cells from leaving the RMS. Within the present project two methods were evaluated with regard to their potential to redirect neuroblasts from the RMS of adult rats towards a nearby brain lesion.Dissertation579 242 - Some of the metrics are blocked by yourconsent settings
Item-typ:Veröffentlichung, Investigation of the "foreign body response" and its pharmacological regulation in chronic intracerebral cannula implantation in rats(2015-12-14); ; ; Chronic brain implants cause a tissue response, also referred to as "foreign body response", which involves the formation of a glial scar as well as progressive neurodegeneration. Both contribute to inconsistent performance of electrodes in the field of brain-computer-interfaces (BCIs). In order to improve the biocompatibility of chronic brain implants and to promote neuronal survival in the vicinity of the implant, the excitotoxic and inflammatory cascades after device implantation were aimed to be suppressed at a very early stage. For this purpose, the uncompetitive NMDA receptor antagonist memantine, the ATP/ADP-hydrolysing enzyme apyrase, and the antibiotic minocycline were locally applied during cannula implantation in the caudal forelimb area (CFA) of the motor cortex (M1) in Lister Hooded rats. The rats' behavioural performance was assessed before and once weekly after cannula implantation in a skilled reaching and a ladder rung walking task as well as in the open field and, moreover, the neuronal and glial distribution in the vicinity of the implant were examined after two and six weeks.Dissertation307 164 - Some of the metrics are blocked by yourconsent settings
Item-typ:Veröffentlichung, Neonatale Läsionen des präfrontalen Cortex der Ratte: Effekte auf die Neurophysiologie des Nucleus accumbens(2004-05-14); ; Neurodevelopmental models of schizophrenia posit that early brain damage leads to dys- or misconnection effects possibly altering synaptic transmission in brain sites distal of the lesion. We tested the hypothesis that neonatal medial prefrontal cortex (mPFC) lesions affects the sensitivity of the mesoaccumbal dopamine (DA) system. Using extracellular single unit recordings combined with systemic application of the DA agonist apomorphine, followed by the D2 receptor antagonist haloperidol or the D1 receptor antagonist SCH23390, we compared electrophysiological properties of nucleus accumbens (NAC) core and shell neurons after bilateral excitotoxic lesions of mPFC induced at postnatal day 7 or in adult rats. Whereas animals with adult mPFC lesions showed an altered discharge pattern within core region, neonatal mPFC lesions altered the discharge pattern within shell region. Subcutaneous administration of apomorphine (4 mg/kg) reduced accumbal firing rate in 77% of all neurons. Onset and magnitude of apomorphine-induced inhibition of neuronal activity was faster and stronger in rats with neonatal but not adult mPFC lesions in both core and shell regions. Apomorphine-induced inhibition was partially reversed by of 0.1 mg/kg haloperidol only in core region of neonatal lesioned rats. Apomorphine-induced excitation of neuronal activity (in 21% of all neurons) was reversed by the D1 receptor antagonist SCH23390 (0.1 mg/kg) in all excited neurons. These data support the hypothesis that neonatal but not adult lesions of mPFC alter cortico-striatal networks and suggest that disturbance of mPFC development leads to neurodevelopmental changes in mesoaccumbal DA system during adulthood.Dissertation269 244 - Some of the metrics are blocked by yourconsent settings
Item-typ:Veröffentlichung, Effekte akuter, lokaler oder chronischer Cannabinoidbehandlung auf die Verhaltensleistung der Ratte(2008-12-12); ; ; The products of the hemp plant Cannabis sativa, marijuana and hashish, belong to the most widely used drugs after alcohol and tobacco. The main psychoactive ingredient of cannabis, tetrahydrocannabinol, and other synthetic cannabinoid receptor agonists produce their neuronal effects via interaction with the cannabinoid CB1-receptor. The molecular characterization of the neuronal CB1- and the CB2-receptor, which is mainly expressed in the immune system, as well as the identification of the endogenous ligand anandamide around 20 years ago, was the beginning of modern cannabinoid research.Recent research yielded fascinating insight into the CB1-receptor distribution in the brain and the role of anandamide or other endocannabinoids as neuromodulators. The endocannabinoid system plays a major role in several cognitive, sensory, and motor functions. Accordingly, the therapeutic potential of compounds affecting this system is now in the focus of psychopharmacological research. Endocannabinoids might also play a role in the pre- and postpubertal development of the brain. Hence, pubertal cannabis use may be involved in the etiopathogenesis of neuropsychiatric disorders.Dissertation259 143 - Some of the metrics are blocked by yourconsent settings
Item-typ:Veröffentlichung, Verhaltenspharmakologische Untersuchungen zur Auswirkung neonataler Läsionen des entorhinalen Cortex auf kognitive Leistungen adulter Ratten(2004-10-15); ; ; The entorhinal cortex (EC) is involved in a variety of cognitive functions by virtue of its neuronal input from the neocortex and projection to the hippocampal formation and the limbic-striatal system. Neonatal lesions are increasingly considered useful models for disconnection syndromes such as schizophrenia. Thus, the effects of neonatal EC lesions on adult rat behavior were investigated. Bilateral neonatal (postnatal day 7) lesions were induced by microinjection of ibotenic acid into the EC. Naïve and sham-lesioned (PBS only) rats served as controls. Adult rats were tested for spatial learning in an 8-arm radial maze and for motivation. Prepulse inhibition (PPI) of the acoustic startle reflex (ASR) and locomotor activity were assessed with and without apomorphine (APO) challenge and before and after repeated MK-801, PPI also after acute low dose MK-801. Finally, the brains were histologically processed to detect brain tissue damage. Neonatal lesions produced thinning of tissue in the EC and reduced myelination and the density of parvalbumin-immunpositive cells in the hippocampus and the amygdala. They increased perseveration only in a delayed task in the radial maze, induced a working memory deficit during an allocentric and egocentric task and also reduced breakpoints in operant responding. Lesions did not alter baseline locomotor activity, but enhanced the locomotor stimulating effect of APO. PPI was not affected by the lesion with and without APO challenge. However, EC-lesions prevented the PPI-disruptive effect of acute low dose MK-801. Locomotor activity was reduced after MK-801 treatment in all groups but no effect on PPI was found. Neonatal lesions of the EC induced neuroanatomical changes, behavioral deficits and dysregulation of dopaminergic and glutamatergic functions that are characteristic in schizophrenic patients. Thus, neonatal lesions of the EC may serve as an animal model for certain aspects of neurodevelopmental disturbances, e.g. schizophrenia.Dissertation260 197 - Some of the metrics are blocked by yourconsent settings
Item-typ:Veröffentlichung, Effekte von Enriched Environment auf strukturelle Veränderungen und Verhaltensdefizite nach neonatalen Läsionen des medialen präfrontalen Cortex bei Ratten(2010-10-13); ; ; In contrast to adult lesions, the ventral medial prefrontal cortex (vmPFC) of rats regenerates after neonatal lesions on postnatal day (PND) 5-12. The present study investigates whether high enriched environment housing conditions (HEE) can attenuate the behavioural deficits which are typically observed after neonatal lesions of the vmPFC. For this purpose rats received bilateral ibotenic acid injections into the vmPFC on PND 7. On PND 21 the rats were dived into a group housed in standard conditions, while the other group was housed in HEE, shamoperated and naïve rats served as controls. While HEE attenuated the vmPFC-lesion induced working memory deficit in the 4-arms baited raialmaze task, and the perseveration behaviour in its reversal, it had no effect on the decreased unconditioned fear in the elevated plus maze. Also HEE seems to have beneficial effects on the performance of neonatal lesioned rats in the food-choice test. Additionally the present study was able to show, that neoatal lesions increase the number of parvalbumine immunoreactive cells in two brain regions interconnected with the vmPFC, namely the basolateral amygdala and the hippocampus.Dissertation841 230 - Some of the metrics are blocked by yourconsent settings
Item-typ:Veröffentlichung, Zur Rolle des cannabinoiden Systems bei konditionierter Furcht der Ratte(2011-03-18); ; ; In recent research the cannabinoide system has been documented as a versatile neuromodulatory system which among other things influences learning and memory. We here applied the paradigm of fear conditioning to study the influence of cannabinoid receptor agonists and antagonists on different phases of learning and memory processes in rats. The prefrontal cortex and the amygdala play a decisive role in the coordination of emotional behavior. In both brain areas cannabinoid receptors (CB1) have already been detected. Through the combination of fear conditioning and specific activation or inhibition of the CB1 receptors in these brain areas new insight on the influence of the cannabinoid system could gained especially on emotional learning and memory processes and their different phases.Dissertation286 431 - Some of the metrics are blocked by yourconsent settings
Item-typ:Veröffentlichung, Do cognitive problems start before motor dysfunction in animal models for Huntington Disease(2013-11-14); ; ; Huntington s disease (HD) is a devastating neurodegenerative disorder caused by a genetic mutation that produces an expansion of C-A-G repeats in the huntingtin (HTT) gene. This expansion results in a selective neuronal degeneration in striatal and cortical brain regions. Although HD is best known for chorea, the disease is actually a triad of progressive cognitive, psychiatric and motor symptoms and patients usually die within 15 to 20 years of onset. Cognitive impairments seem to occur decades prior to the onset of motor symptoms. This potentially offers a long time window for treatments to delay or halt disease progression. Development of such treatments requires the generation of transgenic animal models for HD. Such models are now available and have already greatly enhanced our understanding of the pathogenesis of HD. But unsolved questions such as: "Do cognitive manifestations precede motor deficits in transgenic mouse and rat models for HD?" µremain. We address this question in 3 studies that examine the development of motor, cognitive and psychiatric symptoms in BACHD mice and rats, two recently generated models for HD. Unlike other genetic models, BACHD mice and rats express the full length of the human mutant HTT (97 polyglutamine repeats) and present neuropathology similarities to that of patients. We found progressive motor, cognitive and psychiatric deficits in transgenics BACHD mice and rats compared to their wild type littermate controls, on different tasks such as catwalk, rotarod, open field, zero-maze, cross-maze, prepulse inhibition and fear conditioning. The findings indicate that progressive cognitive deficits can be reliably detected with methodologically rigorous protocols. However some phenotypic variability (body weight and emotional-like behavior, for example) was found and might involve species differences and ectopic expression of the human mutant HTT gene. Finally, the time course for the emergence of the various symptoms indicates that motor abnormalities might be the first to occur in transgenic BACHD mice and rats. In conclusion: we have identified robust cognitive and motor phenotypes for BACHD mice and rats that can be used to test novel compounds from HD drug discovery programs. Certain tests like fear conditioning, lend themselves for translational approaches and characterization of HD patients in such tests would be a logical next step. Confirmation of a fear conditioning phenotype in HD patients would offer an additional functional read-out for drug testing and decrease program risk by bridging the gap between rodent and human testing.Dissertation312 121 - Some of the metrics are blocked by yourconsent settings
Item-typ:Veröffentlichung, Interactions of serotonin2A and metabotropic glutamate2/3 receptors in behavioural control in rats(2011-12-13); ; ; Serotonin (5-hydroxytryptamine, 5-HT)2A and metabotropic glutamate (mGlu2/3) receptors show a strikingly overlapping distribution and share strong behavioural and functional interactions. The thesis investigated the functional relevance of 5-HT2A and mGlu2/3 receptor interactions focussing on two aspects of behavioural inhibition: impulsivity and sensorimotor gating mechanisms. Experiments were conducted in Lister Hooded rats trained in different tests for impulsivity and treated with 5-HT2A and mGlu2/3 receptor ligands. Sensorimotor gating mechanisms were assessed via the prepulse inhibition of the acoustic startle reflex. Taken together, the studies show close antagonistic interactions between 5-HT2A and mGlu2/3 receptors at the behavioural and systems level. The results further suggest that mGlu2/3 receptor agonists have the potential to attenuate impulsivity-related disorders and sensorimotor gating deficits resulting from a hyperserotonergic state.Dissertation284 110