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Function of hippocampal formation in avoidance of a moving object in rat
Zitta, Pavel ; Svoboda, Jan (advisor) ; Blahna, Karel (referee)
In the last decade, there has been a significant shift in hippocampal research from static tasks to dynamic environments that better model real-life animal situations in nature. At the same time, special attention has recently been paid to inhibitory parvalbumin interneurons (PVIs) that modulate hippocampal oscillations. Therefore, the aim of this work was to investigate the role of PVIs in orientation in dynamic environments, or in behavior relative to a potential threat posed by a moving object. In this context, chemogenetic methods were used to allow experimental manipulation of PVIs. In this work, we trained transgenic PV-cre rats in a robot avoidance task. Despite intensive behavioral training, the rats appeared to learn the task only very slowly. Chemogenetic activation of PVI with substance C21 resulted only in increased locomotor activity with a stable robot. The results show that C21 does not otherwise have a major effect on rat behavior, at least not with the relatively low number of hM3Dq expressed in the PVI. Based on local potential recording (LFP) results, we further showed that PVI activation had an effect on theta frequency band power. Keywords: Behavioral task, Hippocampus, Chemogenetics, LFP, Parvalbumin, Robot
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The use of chemogenetic tools in the research of brain diseases
Neřoldová, Markéta ; Stuchlík, Aleš (advisor) ; Tabáková, Petra (referee)
Chemogenetics is a newly developed set of tools that allow for selective manipulation of cell activity. They consist of a receptor mutated irresponsive to endogenous ligands and a synthetic ligand that does not interact with the wild-type receptors. Many different types of these receptors and their respective ligands for inhibition or excitation of neuronal subpopulations were designed in the past few decades. It has been mainly the G-protein coupled receptors (GPCRs) selectively responding to clozapine-N-oxide (CNO), namely Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), that have been employed in research. Chemogenetics offer great possibilities since the activity of the receptors is reversible, inducible on demand by the ligand, and non-invasive. Also, specific groups or types of neurons can be selectively manipulated thanks to the delivery by viral vectors. Furthermore, the effect of the chemogenetic receptors on neurons lasts longer, and even chronic activation can be achieved. That can be useful for behavioural testing. The great advantage of chemogenetic tools is especially apparent in the case of the research of brain diseases since they can manipulate whole neuronal circuits and connections between different brain areas. Many psychiatric or other brain diseases...
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