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Cognitive flexibility in selected animal models of psychiatric disorders
Janíková, Martina ; Stuchlík, Aleš (advisor) ; Rokyta, Richard (referee) ; Ježek, Karel (referee)
Cognitive flexibility is the ability to adjust thinking and behavior based on changing conditions. Cognitive rigidity has been described in a variety of psychiatric and neurodevelopmental disorders and has been suggested to contribute to symptom maintenance. Therefore, we aimed to study cognitive flexibility and other behavioral characteristics in several rodent models relevant to schizophrenia, obsessive-compulsive disorder, and autism spectrum disorder. In a two-hit mice model relevant to schizophrenia, we found the between-group difference in set- shifting and decreased number of parvalbumin interneurons in the hippocampus of stressed female mice. Interestingly, we found no impairment in any other behavioral task. In two pharmacological rat models relevant to OCD, we showed that sensitization to D2/D3 receptor agonist quinpirole and serotonin 1A/7 agonist 8-OH-DPAT produced severe spatial learning and memory impairment in the Active Allothetic Place Avoidance task. The impairment was so severe that the reversal couldn't be tested. Surprisingly, drugs decreasing glutamatergic neurotransmission, memantine and riluzole, further impaired the performance in both models, although no such effect was observed when they were applied alone. Lastly, we showed that the knockout of a collapsin response...
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Hippocampus Dysfunction in Quinpirole Sensitization Model of Obsessive-Compulsive Disorder
Brožka, Hana ; Stuchlík, Aleš (advisor) ; Jendelová, Pavla (referee) ; Kelemen, Eduard (referee)
Obsessive-compulsive disorder (OCD) is a serious psychiatric condition manifested by repeated thoughts followed by stereotypic compulsive behavior. Alterations to cortico-thalamo-striato- cortical circuits are most often implicated in the pathophysiology of OCD. However, many studies have also found a changed volume, shape and activity of the hippocampus in OCD patients. This work focused on the activity of hippocampal CA1 cells during stereotypical checking behavior and on cognitive flexibility in a quinpirole (QNP) sensitization model of OCD. The activity of CA1 hippocampal cells during stereotypical checking was assessed in an enriched open-field test in QNP sensitized rats. Arc+ (activity-regulated cytoskeletal associated protein, or Arg 3.1) mRNA expression profiles were determined in CA1 coronal hippocampal sections following stereotypical checking. After the establishment of stereotypical checking (10 sessions), rats were exposed to the arena and sacrificed after 5 minutes. QNP sensitized animals visited the same objects with the same frequency as during previous sessions, while control rats did not. Locomotor activity was comparable between QNP treated rats and controls. Following sacrifice, rat brains were flash frozen and sliced to 20 µm thick sections. Sections, mounted on slides, were hybridized...
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Studying the role of striatal cholinergic signaling in control of behaviour and behavioural flexibility
Tyshkevich, Alexandra ; Janíčková, Helena (advisor) ; Levčík, David (referee)
Cognitive flexibility is an important mechanism enabling organisms to adapt to their changing environment. Different brain structures are involved in this complex process. It has been repeatedly shown that the striatum is one of the key structures controlling cognitive flexibility. Striatum receives rich input from different brain regions while its output is rather uniform. Striatal functions and signalling are greatly modulated by dopamine and acetylcholine. A number of studies have shown involvement of striatal acetylcholine and its receptors in the control of cognitive flexibility but very little is known about the role of M4 muscarinic acetylcholine receptors. These receptors are inhibitory, and they have been shown to induce long-term depression in striatal medium spiny neurons, therefore opposing the action of the dopamine D1 receptors. We hypothesize that the inhibitory effect of M4 muscarinic acetylcholine receptors may supress spiny projection neurons coding for outdated and no longer effective behavioural strategy and thus they may be necessary for the flexible change of behaviour. In the present thesis, I investigated the effects of pharmacological antagonism of M4 receptors on cognitive flexibility of mice tested in a simple reversal learning paradigm. Key words: striatum; cholinergic...
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Cholinergic signaling in the striatum and its significance in cognitive flexibility
Smolík, Matyáš ; Janíčková, Helena (advisor) ; Funda, Jiří (referee)
In the striatum, cholinergic interneurons (CINs) contribute to the control of behaviour, motor and cognitive functions. Recently, number of studies have shown a special significance of CINs in the control of cognitive flexibility: the ability to learn new behavioural strategies when requirements of the environment change. Along with working memory, cognitive inhibition, attention control and other cognitive domains, cognitive flexibility belongs to executive functions. Cognitive flexibility impairment is present in a range of neuropsychiatric disorders and thus, understanding its mechanisms is of outstanding importance. The proposed work will first describe anatomy and cellular composition of the striatum and its functions. It will further describe cholinergic system with a special attention to cholinergic signalling in the striatum. The final chapter of the general part of the thesis will focus on cognitive flexibility. After discussing the involved structures and systems separately, the thesis will eventually provide comprehensive review of currently available studies investigating how striatal CINs contribute to brain's ability to replace old concepts with new and more efficient ones.
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Hippocampus Dysfunction in Quinpirole Sensitization Model of Obsessive-Compulsive Disorder
Brožka, Hana ; Stuchlík, Aleš (advisor) ; Jendelová, Pavla (referee) ; Kelemen, Eduard (referee)
Obsessive-compulsive disorder (OCD) is a serious psychiatric condition manifested by repeated thoughts followed by stereotypic compulsive behavior. Alterations to cortico-thalamo-striato- cortical circuits are most often implicated in the pathophysiology of OCD. However, many studies have also found a changed volume, shape and activity of the hippocampus in OCD patients. This work focused on the activity of hippocampal CA1 cells during stereotypical checking behavior and on cognitive flexibility in a quinpirole (QNP) sensitization model of OCD. The activity of CA1 hippocampal cells during stereotypical checking was assessed in an enriched open-field test in QNP sensitized rats. Arc+ (activity-regulated cytoskeletal associated protein, or Arg 3.1) mRNA expression profiles were determined in CA1 coronal hippocampal sections following stereotypical checking. After the establishment of stereotypical checking (10 sessions), rats were exposed to the arena and sacrificed after 5 minutes. QNP sensitized animals visited the same objects with the same frequency as during previous sessions, while control rats did not. Locomotor activity was comparable between QNP treated rats and controls. Following sacrifice, rat brains were flash frozen and sliced to 20 µm thick sections. Sections, mounted on slides, were hybridized...
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Flexibility in spatial cognition of rat
Staňková, Anna ; Svoboda, Jan (advisor) ; Telenský, Petr (referee)
5 Abstract Cognitive flexibility is an ability to adapt a behavior according to a dynamic changes in an environment. It belongs to executive functions, along with the processes of working memory, attention, motivation and others. Flexibility is important in the process of changing "stimulus-response" contingency at the time when the initial stimulus no longer leads to reward. According to the nature of the changes we can distinguish three types of cognitive flexibility: reversal learning, intradimensional set shifting and extradimensional set shifting. The processes of cognitive flexibility take place in fronto-striato-thalamic circuit with numerous connections to other brain regions, especially the limbic system. Deficit in cognitive flexibility belongs among cognitive symptoms of schizophrenia, a psychiatric illness we studied in the experimental part of this work using its analogue in rat. The aim of the experimental work was to test cognitive flexibility deficit in the rat model of schizophrenia-like behavior in the Carousel maze in four versions of task with different cognitive load. Animal model of schizophrenia was induced by acute administration of non-competitive NMDA receptor antagonist MK-801 at doses of 0.05 and 0.10 mg/kg i.p. Reversal learning was not damaged in this type of task following the...
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