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Localization of GABAB receptor in the mouse dorsal cochlear nucleus and auditory cortex under physiological and pathological conditions
Melichar, Adolf ; Králíková, Michaela (advisor) ; Malínský, Jan (referee)
GABAB receptors play an important role in regulation of neuronal excitability and stability of neural microcircuits. It is well known that dysregulation of slow GABAergic signalisation can lead to many pathological conditions (epilepsy, anxiety etc.). Current research indicates that the imbalance in the inhibitory transfer, caused by changes in the expression of GABABR in the auditory system could play an important role in the progression of tinnitus. The goal of the present thesis was to determine the distribution of the GABAB receptor and its auxiliary subunit KCTD12 in the mouse auditory cortex and the dorsal cochlear nucleus (DCN). Furthermore, a change in GABAB receptor localization in the DCN was observed in mice exposed to an acoustic stress. The GABAB receptor was expressed across the entire auditory cortex, both on the body and on the neuronal fibres. On the contrary, KCTD12 was found only in a particular subgroup of neurons that includes VIP (vasoactive intestinal peptide) and cholecystokinin positive interneurons., GABABR and KCTD12 protein were found in all layers and in all studied cells types (fusiform, cartwheel and stellate) of the DCN. Acoustic trauma of the WT mice resulted in GABAB receptor internalization specifically in fusiform cells that are the main projection neurons of the...
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Molecular mechanisms of the glycinergic signalization in the central nervous system
Melichar, Adolf ; Králíková, Michaela (advisor) ; Ladislav, Marek (referee)
The amino acid neurotransmitter glycine, which mediates the inhibitory transmission and regulates the excitatory signalization, is found in many regions of the central nervous system. It is produced especially the spinal cord and the brainstem, where glycine activates the presynaptic and postsynaptic Gly receptors (GlyR). In other regions of the brain, glycine is released in the area of occurrence of NMDA receptors (NMDAR), which it activates together with the excitatory neurotransmitter glutamate. The binding of the glycine leads to the opening of the channel of these ionotropic receptors and thus also to a change in the electrochemical properties of the membrane, such as permeability for Ca2+ ions, membrane potential and shunting. The expression of different subunits of NMDAR and GlyR is specific in terms of location and time, which enables various responses to the presence of glycine in the synaptic cleft and its surroundings. The concentration of glycine in synaptic cleft and glycinergic terminals is controlled especially by glycine transporters (GLYT), that are found in two functionally different types. The destabilisation of the equilibrium and signal mechanisms of glycine may lead to serious diseases such as hyperekplexia that can be caused by mutations in the glycine receptors and...
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