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Role of ventral hippocampus and medial prefrontal cortex in behavioral flexibility in rodents
Černotová, Daniela ; Svoboda, Jan (advisor) ; Telenský, Petr (referee)
Behavioral adaptation to a continuously changing environment is critical for the survival of the animals, but also day-to-day interactions in the human world. The main components maintaining flexibility in cognition and behavior are well-established and depend mostly on proper intercommunication within the prefrontal cortex (PFC) and striatum. Some parts of the PFC are densely innervated by the ventral hippocampus (vHPC), which has a great impact on its functioning. Also, hippocampal-prefrontal circuit dysfunction has been shown to disrupt the integrity of flexible cognition in some neuropsychiatric diseases. Therefore, the exact functional role of this pathway is an indispensable part of the research. The aim of this study was to test the role of the vHPC and the medial PFC (mPFC) in an active place avoidance task on a rotating arena in 1) two flexibility task variants - reversal learning and set- shifting - and 2) the spatial memory retrieval. We inactivated these structures by muscimol (GABAA receptor agonist) in a variety of unilateral, bilateral, and combined local injections. Disrupted performance was apparent in reversal learning in vHPC-inactivated rats. No effect was seen in mPFC-inactivated rats. Impairments after the task acquisition were observed in bilateral vHPC and mPFC inactivations...
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Vliv klomipraminu a risperidonu na učení a flexibilitu u animálního modelu obsedantně kompulzivní poruchy
Radostová, Dominika ; Stuchlík, Aleš (advisor) ; Kopřivová, Jana (referee)
Chronic sensitization of dopamine D2/D3 receptors by agonist quinpirole (QNP) induces compulsive checking behaviour in rats, which is considered an animal model of obsessive-compulsive disorder (OCD). Previous study revealed deficit in cognitive flexibility in QNP sensitized rats. This thesis focused on determining if this cognitive flexibility deficit is ameliorated by co-administration of clomipramine (CMI), risperidone (RIS) or combination of both (CMI+RIS) to QNP treatment. Aversively motivated active place avoidance task on a Carousel maze with reversal was used. The number of entrances into a to-be-avoided shock sector was evaluated as measure of performance. Six treatment groups were used: control group, QNP group, CMI group, QNP/CMI combination, QNP/RIS combination and QNP/CMI/RIS combination. Surprisingly, when compared alone, significantly worse acquisition was observed for QNP group compared to control group. However, similarly to previous study, QNP group had a worse performance in a first reversal session compared to control group. When all groups were compared, only QNP/CMI group had worse initial learning compared to control group. In reversal learning, only QNP treated group had a significantly more entrances than control group in first reversal session. Results suggest that co-treatment...
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Role of ventral hippocampus and medial prefrontal cortex in behavioral flexibility in rodents
Černotová, Daniela ; Svoboda, Jan (advisor) ; Telenský, Petr (referee)
Behavioral adaptation to a continuously changing environment is critical for the survival of the animals, but also day-to-day interactions in the human world. The main components maintaining flexibility in cognition and behavior are well-established and depend mostly on proper intercommunication within the prefrontal cortex (PFC) and striatum. Some parts of the PFC are densely innervated by the ventral hippocampus (vHPC), which has a great impact on its functioning. Also, hippocampal-prefrontal circuit dysfunction has been shown to disrupt the integrity of flexible cognition in some neuropsychiatric diseases. Therefore, the exact functional role of this pathway is an indispensable part of the research. The aim of this study was to test the role of the vHPC and the medial PFC (mPFC) in an active place avoidance task on a rotating arena in 1) two flexibility task variants - reversal learning and set- shifting - and 2) the spatial memory retrieval. We inactivated these structures by muscimol (GABAA receptor agonist) in a variety of unilateral, bilateral, and combined local injections. Disrupted performance was apparent in reversal learning in vHPC-inactivated rats. No effect was seen in mPFC-inactivated rats. Impairments after the task acquisition were observed in bilateral vHPC and mPFC inactivations...
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Protective effect of pro-cognitive training during adolescence on neuronal coordination deficit in a pharmacological model of schizophrenia.
Krajčovič, Branislav ; Kubík, Štěpán (advisor) ; Bendová, Zdeňka (referee)
Schizophrenia is a severe neuropsychiatric disorder characterized by positive, negative and cognitive symptoms with poor functional outcomes, placing an enormous burden on the individual, caregivers and society. Although deficits in cognition are an integral part of the disease and the best predictor of functional outcomes, there is as yet no established treatment addressing them. Avoidance of a hidden place on a continuously rotating arena (Carousel) requires cognitive control and is a rodent model of cognitive coordination of information from dissociated spatial frames, which is impaired in acute pharmacological and neurodevelopmental model of schizophrenia. Cognitive training on the Carousel during adolescence alleviates adult cognitive deficit in a neurodevelopmental model of schizophrenia and improves neural coordination (oscilations in the beta and gamma band), which is thought to be necessary for cognition. We examined if cognitive training during adolescence eliminates the deficit in neuronal coordination observed in adult rats after acute systemic NMDA receptor antagonist MK-801 (0.15 mg/kg). During adolescence, rats were either trained in spatial avoidance on Carousel or merely handled. As adults, rats received two 5-min exploration sessions in the same (A/A) or in two distinct...
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Vliv klomipraminu a risperidonu na učení a flexibilitu u animálního modelu obsedantně kompulzivní poruchy
Radostová, Dominika ; Stuchlík, Aleš (advisor) ; Kopřivová, Jana (referee)
Chronic sensitization of dopamine D2/D3 receptors by agonist quinpirole (QNP) induces compulsive checking behaviour in rats, which is considered an animal model of obsessive-compulsive disorder (OCD). Previous study revealed deficit in cognitive flexibility in QNP sensitized rats. This thesis focused on determining if this cognitive flexibility deficit is ameliorated by co-administration of clomipramine (CMI), risperidone (RIS) or combination of both (CMI+RIS) to QNP treatment. Aversively motivated active place avoidance task on a Carousel maze with reversal was used. The number of entrances into a to-be-avoided shock sector was evaluated as measure of performance. Six treatment groups were used: control group, QNP group, CMI group, QNP/CMI combination, QNP/RIS combination and QNP/CMI/RIS combination. Surprisingly, when compared alone, significantly worse acquisition was observed for QNP group compared to control group. However, similarly to previous study, QNP group had a worse performance in a first reversal session compared to control group. When all groups were compared, only QNP/CMI group had worse initial learning compared to control group. In reversal learning, only QNP treated group had a significantly more entrances than control group in first reversal session. Results suggest that co-treatment...
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Impaired cognitive coordination on a rotating arena after systemic dizocilpine (MK-801).
Buchtová, Helena ; Kubík, Štěpán (advisor) ; Olexová, Lucia (referee)
Disruption of cognitive abilities such as learning, memory and spatial navigation accompanies a number of neuropsychiatric disorders including schizophrenia. Cognitive symptoms are also most difficult to target by available pharmacotherapy.. Behavioral and molecular evidence point to a disruption of NMDA receptors and glutamatergic and dopaminergic neurotransmission. Impaired cognitive coordination has been proposed as a core cognitive deficit in schizophrenia. Non- competitive NMDAR antagonists are used to model schizophrenia- related symptoms in humans and in experimental animals. Place avoidance on a rotating arena is used to model cognitive functions disrupted in an animal model of schizophrenia. The goal of this thesis is to show whether the deficit in place avoidance is due to disrupted cognitive coordination or another effect of NMDAR antagonism such as hyperlocomotion, general learning deficit, or altered sensitivity.
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