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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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Brain Oscillations and Temporal Structure of Spatial Memory Pattern Retrieval
Zitrický, František ; Ježek, Karel (advisor) ; Kelemen, Eduard (referee) ; Vlček, Kamil (referee)
The hippocampus is a brain structure essentially involved in episodic memory, spatial navigation and other complex cognitive functions. The distinct network architecture of hippocampal CA3 allows to combine converging sensory inputs in creation of complex neural representations. The hippocampus further interacts with the entorhinal cortex to organize knowledge into relational representations, also known as 'cognitive maps'. In rodents, the hippocampal pyramidal neurons behave as place cells, where a neuron is active whenever the subject occupies specific location in the environment. The collective activity of the place cells represents a neural map that is reinstated during repeated exploration of the same space. The place cell maps are thus recognized as neural substrate of spatial memory. In this work, we aimed at better understanding of hippocampal CA3 network dynamics during period of reinstatement of the appropriate place cell representation. We thus analysed CA3 place cell activity recorded during 'teleportation' experiment, where the rats are exposed to abrupt changes in spatial context identity. As shown previously, the network state transitions involve short competitive period, where network state quickly switches between the representations of the previous and the present environment. We...
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Circadian clock in the hippocampus
Liška, Karolína ; Sumová, Alena (advisor) ; Riljak, Vladimír (referee) ; Ježek, Karel (referee)
To adapt to the daily changing environment, living organisms on Earth have developed an inner clock. In mammals, the clocks are organized in a circadian system which is governed by the central oscillator in suprachiasmatic nuclei (SCN) and consists of peripheral oscillators located in tissues and organs throughout the body. The synchrony of the entire system allows proper alignment of physiological processes to the optimal time of day. It was shown that cognitive performance and memory formation are also subjected to daily variations and many brain regions involved in these processes, especially hippocampus (HPC), were recently found to harbor circadian clocks. Nevertheless, the precise function of these clocks and the mechanism of their synchronization to the external conditions remain to be elucidated. The focus of my PhD thesis was a detailed analysis of the circadian clocks in rodent HPC. We aimed to characterize the oscillators in distinct HPC subregions, identify signals responsible for their synchronization and compare the HPC clock properties to those of the clock in the choroid plexus (CP) which is the adjacent non-neuronal structure. Moreover, we examined the role of clocks in HPC and other brain regions in the process of memory formation, focusing on time memory acquisition. First, we...
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The importance of NMDA antagonists in animal models of ischemic injury and major depressive disease
Kletečková, Lenka ; Valeš, Karel (advisor) ; Zach, Petr (referee) ; Ježek, Karel (referee)
Glutamatergic system is the main excitatory system and glutamatergic receptors are the most abundantly expressed in whole central nervous system. The most widespread type of glutamatergic receptors are N-methyl-D-aspartate (NMDA) receptors which are essential for physiological development of nervous tissue, synaptic plasticity and cognitive processes. On the other hand, over-activation of these receptors leads to excitotoxic damage of nervous tissue and serious neurological consequences for future quality of life. Disruption of glutamatergic system is common feature for hypoxic-ischemic damage, traumatic brain injury, neurodegenerative and neuropsychiatric diseases. Therefore glutamatergic system and specifically NMDA receptors are an attractive target for neuropharmacological research. Presented thesis explores the effect of several molecules with modulating inhibiting effect on NMDA receptor. Work is preferentially focused on application research; the main aim is evaluated therapeutic potential of studied compounds. First group of compounds is represented by neuroactive steroids pregnanolone glutamate and pregnanolone hemipimelate, which are allosteric inhibitors of NMDA receptor. Here, their neuroprotective effect is demonstrated in hypoxic-ischemic and excitotoxic damage of nervous tissue....
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The Processing of Social Information by Neurons in the Rat's Hippocampus.
Hanzlík, Adam-František ; Kelemen, Eduard (advisor) ; Ježek, Karel (referee)
ABTRACT In order to survive, an animal must be able to integrate vital information about it's surroundings, such as information about the environment and the social interactions therein. Decades of research have established the hippocampal formation as a structure indispensable for spatial memory. It was only recently, though, that evidence has emerged suggesting that the hippocampus, most notably the dorsal CA2 region, also supports the encoding of social information. New behavioural as well as electrophysiological evidence appeared, highlighting the importance of sleep for the processing of social information. In my thesis, I used microelectrodes to record the electrophysiological activity of individual CA2 neurons from freely-moving rats, during wake as well as in sleep. In order to study the processing of social information by hippocampal neurons, I employed a novel experimental paradigm in which social stimulation, in the form of two rat conspecifics, was presented in a spatial context. I report that the discharge of some CA2 neurons was organised within the experimental maze, even after social stimulation was added. Moreover, I observed that the spatial activity of neurons changed after the addition of social stimuli, and that it further changed when the location of the two conspecifics was shuffled....
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The importance of NMDA antagonists in animal models of ischemic injury and major depressive disease
Kletečková, Lenka ; Valeš, Karel (advisor) ; Zach, Petr (referee) ; Ježek, Karel (referee)
Glutamatergic system is the main excitatory system and glutamatergic receptors are the most abundantly expressed in whole central nervous system. The most widespread type of glutamatergic receptors are N-methyl-D-aspartate (NMDA) receptors which are essential for physiological development of nervous tissue, synaptic plasticity and cognitive processes. On the other hand, over-activation of these receptors leads to excitotoxic damage of nervous tissue and serious neurological consequences for future quality of life. Disruption of glutamatergic system is common feature for hypoxic-ischemic damage, traumatic brain injury, neurodegenerative and neuropsychiatric diseases. Therefore glutamatergic system and specifically NMDA receptors are an attractive target for neuropharmacological research. Presented thesis explores the effect of several molecules with modulating inhibiting effect on NMDA receptor. Work is preferentially focused on application research; the main aim is evaluated therapeutic potential of studied compounds. First group of compounds is represented by neuroactive steroids pregnanolone glutamate and pregnanolone hemipimelate, which are allosteric inhibitors of NMDA receptor. Here, their neuroprotective effect is demonstrated in hypoxic-ischemic and excitotoxic damage of nervous tissue....
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