|
|
Stereological quantification of striatal NPY-positive interneurons and their genetic modification by the AAV5 viral vector
Smolík, Matyáš ; Janíčková, Helena (advisor) ; Chvojková, Markéta (referee)
Different types of interneurons in the striatum are still relatively poorly understood, especially compared to other parts of the brain such as the cortex or hippocampus. One of the lesser-known types of striatal interneurons that has received increasing attention recently, are neuropeptide Y-expressing interneurons (NPY+ interneurons). Available work indicates that these interneurons are controlled by striatal cholinergic interneurons and thus they may serve as mediators of cholinergic modulation in the striatum. The first aim of this thesis is to determine the absolute number of NPY+ interneurons in the mouse dorsal striatum by stereology, using a transgenic mouse model that shows GFP expression in NPY+ neurons. The second aim of this thesis is to use stereology to determine the volume of the dorsal striatum that we are able to target with viral expression when using a standard stereotactic injection protocol commonly used in our laboratory. The third aim of this study is to test the behavioural effect of knock down of the beta2 subunit of the nicotinic acetylcholine receptor expressed by NPY+ interneurons in the dorsal striatum. The work should serve as a first step in a study that will ultimately allow us to develop a quantitative idea of the absolute and relative number of NPY+ interneurons in...
|
|
| |
|
|
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...
|
|
|
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.
|
|
|
Muscarinic acetylcholine transmission and Alzheimer's disease
Janíčková, Helena ; Doležal, Vladimír (advisor) ; Blahoš, Jaroslav (referee) ; Rokyta, Richard (referee)
Impairment of the cholinergic neurotransmission system is regularly detected in animal models of Alzheimer's disease as well as in human patients suffering from this serious disease. Moreover, there is increasing amount of evidence suggesting that activation of individual mAChR subtypes specifically influences the cleavage of APP, the precursor for β-amyloid. APP can be processed in an amyloidogenic or non-amyloidogenic pathway and a relative abundance of these patways contributes to establishing the final concentration of neurotoxic β-amyloid in the brain. In this work, I have studied the acute and chronic effects of A β1-42 on binding and functional characteristics of mAChR. I have demonstrated that Aβ1-42 present in cell culture expressing the individual subtypes of mAChR negatively and specifically influences the function of the M1 mAChR subtype. I have also detected a decline in muscarinic receptor-mediated signal transduction in brain tissue of young adult APPswe/PS1dE9 mice, a commonly used animal model of Alzheimer's disease. Demonstration of the impairment of muscarinic transmissin in transgenic mice by soluble β-amyloid that occurs earlier than amyloid pathology and behavioral deficit, and its imitation by soluble Aβ1-42 in vitro lend strong support to the notion of the early involvement...
|
|
| |
guest ::
