Balázs, PálMaamrah, Baneen2025-10-212025-10-212025https://hdl.handle.net/2437/398069Our previous in vitro research demonstrated that neuromodulatory actions on astrocytes in the mesopontine region can lead to tonic excitability changes dependent on metabotropic glutamate and N-methyl-D-aspartate receptors. To investigate the in vivo significance of these findings, we conducted a study using chronic chemogenetic activation of mesopontine astrocytes in young adult male mice. In chronic study, we compared a control group, where mesopontine astrocytes expressed only the mCherry fluorescent tag, to a group expressing the hM3D(Gq) chemogenetic actuator. We conclude that chronic astrocytic activation significantly decreased neuronal numbers in the mesopontine region. Cholinergic neuron numbers were reduced to 54% of control levels, while non-cholinergic neuron numbers dropped to 76%. These findings suggest that chronic astrocytic overactivation, and the subsequent neuronal loss, contributes to disturbances in movement and circadian activity, which resemble brain-related symptomes of PSP. This raises a compelling hypothesis: astrocytic overactivation may play a role in the pathogenesis of PSP. In KCNQ study, the KCNQ4 is crucial for regulating neuronal excitability, which is involved in the startle reflex. We investigated how the deleted of the KCNQ4 subunit affects the acoustic startle reflex. We found that KCNQ4 knockout mice exhibited a significantly increased acoustic startle reflex. The findings suggest that the amplified startle reflex observed in KCNQ4 knockout animals is likely due to a combination of cochlear damage and altered neuronal excitability within the brain's startle networks.100enPedunculopontine nucleus (PPN), designer receptor exclusively activated by designer drug (DREEAD), KCNQ4 (Kv7.4), astrocyte, acetylcholine (AC), Mesopontine Regions (MR), non- syndromic hearing loss (DFNA2), acoustic startle reflex (ASR), cuneiform nucleus (CnF).PhD, doktori értekezésElméleti orvostudományokOrvostudományok