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Neuroplasticity in the brain is dynamically controlled in space and time. Different permissive factors and molecular brakes establish and eventually stabilize optimal functional networks in such a way that they are still capable to adapt in response to experience. The visual cortex has been a valuable research model to study neocortical development, function and plasticity from mice to men. For instance, partial loss of vision by monocular enucleation (ME) early in life and in adulthood has been linked to widespread structural and functional reorganization in the visual cortex after short- and long-term survival times. However, the deprivation effects in ages that represent adolescence and cortical changes along the full extent of the visual and non-visual cortices are often overlooked. In that regard we initiated this doctoral project to fulfill these shortcomings. In adult mice, complete reactivation of deprived visual cortex involves an early visually driven recovery followed by multimodal plasticity 3 to 7 weeks post-ME and had been discovered at the beginning of this investigation. We have specifically investigated the age dependence of the onset and the exact timing of both ME-induced reactivation processes by comparing cortical activity patterns of mice enucleated at postnatal day 45 (adolescence) or 120 (adult). Radioactive in situ hybridization for the activity reporter gene zif268 in the visual cortex of adolescent and adult ME mice revealed striking differences. A swifter open-eye potentiated reactivation, between 3 and 5 days, characterized the binocular visual cortex of adolescent mice yet even after 7 weeks, the reactivation remained incomplete, especially in the medial monocular cortex. Consequently, we wondered to what extent monocular enucleation in mice of intermediate age group would induce enucleation-enabled plasticity. In comparison to adolescence, emergent cross-modal participation was demonstrated in P90 animals, although robust reactivation similar to enucleated adults was not achieved yet. Concomitantly, 7 weeks post-ME, somatosensory and auditory cortex shifted from a hypoactive state in adolescence to hyperactivity in adulthood. Thus, we provide evidence for a pre-sensitive period in which gradual recruitment of cross-modal recovery upon long-term monocular enucleation coincides with the transition from adolescence to adulthood in mice. In other words, the cross-modal recruitment of visual cortex following late onset vision loss, at least for monocular enucleation, is stronger in adults.Since the cellular and molecular players that regulate co-occurrence of uni- and cross-modal plasticity specifically in adulthood remain largely elusive, a second aim of this thesis was to apply dark exposure, a housing strategy known to shift the cortical excitation-inhibition balance, as a tool to study the role of the GABAergic system in the age-dependent aspect of ME-induced plasticity. We examined if dark exposure has an impact on the visual cortex reactivation by placing mice in total darkness for 10 days prior to monocular enucleation. Intriguingly, dark exposure converted the outcome of monocular enucleation in adult mice into a more adolescent-like response. A permanent deficit in neuronal activity was detected, most likely reflecting the absence of the cross-modal facet of reactivation due to dark exposure. At the molecular level, monocular enucleation preferentially decreased vGAT levels and induced more GABA production via increased GAD65 and GAD67 levels in the medial monocular cortex. Yet these changes at the presynaptic site were independent of age or dark exposure. However, at the postsynaptic site, elevated levels of the GABAA receptor alpha 1 subunit (mediating phasic inhibition) but not the delta subunit (mediating tonic inhibition), specifically characterized incomplete reactivation like in dark exposed and adolescent mice. Together, our molecular observations put the level of intracortical phasic inhibition forward as an important permissive factor for the age- and experience-dependent cross-modal response to long-term monocular enucleation.To conclude, monocular enucleation as well as dark exposure in the mouse will definitely be outstanding animal models to further decipher the cellular and molecular basis for the age- and experience-dependent response of the visual cortex to deprivation or lesions. In addition, they can enrich our understanding of cross-modal interactions and plasticity, in the emerging context of a high incidence of multimodal neurons and areas in the rodent and higher-order mammalian neocortex, including human.
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Academic collection --- 599.323.4 --- 591.48 --- Muridae. Mice. Rats. Hamsters. Voles. Lemmings. Field-mice. House-mice. Gerbil. Water-rat. Ondatra --- Nervous system --- Theses --- 591.48 Nervous system --- 599.323.4 Muridae. Mice. Rats. Hamsters. Voles. Lemmings. Field-mice. House-mice. Gerbil. Water-rat. Ondatra
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633.877 --- 599.323.4 <480> --- Conifers. Fir bark. Hemlock bark. Larches. Pines. Phylloclades (e.g. emblic) --- Muridae. Mice. Rats. Hamsters. Voles. Lemmings. Field-mice. House-mice. Gerbil. Water-rat. Ondatra--Finland --- 599.323.4 <480> Muridae. Mice. Rats. Hamsters. Voles. Lemmings. Field-mice. House-mice. Gerbil. Water-rat. Ondatra--Finland --- 633.877 Conifers. Fir bark. Hemlock bark. Larches. Pines. Phylloclades (e.g. emblic)
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Brain --- Rats --- Cerveau --- embryology --- atlases. --- Atlases. --- Anatomy --- Development. --- Atlas --- Anatomie --- 591.481.1 --- 599.323.4 --- 591.3 --- Brain of vertebrates. Encephalon. Cerebellum --- Muridae. Mice. Rats. Hamsters. Voles. Lemmings. Field-mice. House-mice. Gerbil. Water-rat. Ondatra --- Animal embryology. Animal ontogeny. Development of the individual organism --- 591.3 Animal embryology. Animal ontogeny. Development of the individual organism --- 599.323.4 Muridae. Mice. Rats. Hamsters. Voles. Lemmings. Field-mice. House-mice. Gerbil. Water-rat. Ondatra --- 591.481.1 Brain of vertebrates. Encephalon. Cerebellum --- Rat --- Muridae --- Atlases --- Anatomy&delete& --- Development --- Monograph
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591.477 --- 591.478 --- 59.084 --- 636.91 --- 636.92 --- 599.323.4 --- Skin. Suckers. Mantle (in Mollusca etc.) --- Keratinous formations. Hair. Bristles. Prickles. Claws. Talons. Hoofs. Feathers. Scales. Horns --- Laboratory animals --- Guinea-pigs (cavies) --- Domestic rabbits --- Muridae. Mice. Rats. Hamsters. Voles. Lemmings. Field-mice. House-mice. Gerbil. Water-rat. Ondatra --- 599.323.4 Muridae. Mice. Rats. Hamsters. Voles. Lemmings. Field-mice. House-mice. Gerbil. Water-rat. Ondatra --- 636.92 Domestic rabbits --- 636.91 Guinea-pigs (cavies) --- 59.084 Laboratory animals --- 591.478 Keratinous formations. Hair. Bristles. Prickles. Claws. Talons. Hoofs. Feathers. Scales. Horns --- 591.477 Skin. Suckers. Mantle (in Mollusca etc.)
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Animals, Laboratory. --- Mice, Nude. --- Research. --- 57.085.1 --- 599.323.4 --- Medicine, Experimental --- Nude mouse --- Zoology, Experimental --- Experimental zoology --- Zoology --- Athymic mice --- Athymic mouse --- Nu nu mouse --- Thymus-aplastic mice --- Thymus-aplastic mouse --- Thymusless mouse --- Laboratory animals --- Mice --- Experimental medicine --- Medicine --- Laboratory Research --- Research Activities --- Research and Development --- Research Priorities --- Activities, Research --- Activity, Research --- Development and Research --- Priorities, Research --- Priority, Research --- Research Activity --- Research Priority --- Research, Laboratory --- Ethics, Research --- Mouse, Athymic --- Mouse, Nude --- Athymic Mice --- Mice, Athymic --- Nude Mice --- Athymic Mouse --- Nude Mouse --- Laboratory Animals --- Animal, Laboratory --- Laboratory Animal --- Disease Models, Animal --- On living organisms or tissues,in vivo (in situ) --- Muridae. Mice. Rats. Hamsters. Voles. Lemmings. Field-mice. House-mice. Gerbil. Water-rat. Ondatra --- Research --- Biomedical Research --- 599.323.4 Muridae. Mice. Rats. Hamsters. Voles. Lemmings. Field-mice. House-mice. Gerbil. Water-rat. Ondatra --- 57.085.1 On living organisms or tissues,in vivo (in situ) --- Animals, Laboratory --- Mice, Nude
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Mice. --- Experimental Neoplasms --- Experimental Neoplasm --- Neoplasm, Experimental --- Cancer of the Liver --- Cancer, Hepatocellular --- Hepatic Neoplasms --- Hepatocellular Cancer --- Neoplasms, Hepatic --- Neoplasms, Liver --- Cancer of Liver --- Hepatic Cancer --- Liver Cancer --- Cancer, Hepatic --- Cancer, Liver --- Cancers, Hepatic --- Cancers, Hepatocellular --- Cancers, Liver --- Hepatic Cancers --- Hepatic Neoplasm --- Hepatocellular Cancers --- Liver Cancers --- Liver Neoplasm --- Neoplasm, Hepatic --- Neoplasm, Liver --- Mice, Laboratory --- Mouse --- Mouse, House --- Mouse, Laboratory --- Mouse, Swiss --- Mus domesticus --- Mus musculus domesticus --- Swiss Mice --- Mice, House --- Mus --- Mus musculus --- House Mice --- House Mouse --- Laboratory Mice --- Laboratory Mouse --- Mice, Swiss --- Swiss Mouse --- domesticus, Mus musculus --- Liver neoplasms --- MICE --- NEOPLASMS --- EXPERIMENTAL --- Experimental --- Liver Neoplasms. --- Neoplasms, Experimental. --- Mice --- Neoplasms --- Liver Neoplasms --- Neoplasms, Experimental
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591.4 --- 57.089.7 --- 639.231 --- 597.8 --- 599.323.4 --- 599.325.1 --- 595.142.39 --- 595.384.16 --- 595.722 --- 594.142 --- 594.382.4 --- 595.132.8 --- 597.1 --- 597.1 Acrania (Leptocardia). Branchiostomidae. Lancelets --- Acrania (Leptocardia). Branchiostomidae. Lancelets --- 595.384.16 Astacidae. Astacus --- Astacidae. Astacus --- 595.142.39 Lumbricidae --- Lumbricidae --- 599.325.1 Leporidae. Rabbits. Hares --- Leporidae. Rabbits. Hares --- 599.323.4 Muridae. Mice. Rats. Hamsters. Voles. Lemmings. Field-mice. House-mice. Gerbil. Water-rat. Ondatra --- Muridae. Mice. Rats. Hamsters. Voles. Lemmings. Field-mice. House-mice. Gerbil. Water-rat. Ondatra --- 597.8 Anura (Salientia). Tailless amphibians --- Anura (Salientia). Tailless amphibians --- 639.231 Selachii. Sharks. Tope. Dogfish (rock salmon) --- Selachii. Sharks. Tope. Dogfish (rock salmon) --- 57.089.7 Necropsy. Dissection techniques --- Necropsy. Dissection techniques --- 591.4 Study of animal organs. Animal organology. Animal anatomy. Zootomy --- Study of animal organs. Animal organology. Animal anatomy. Zootomy --- Blattodea. Blattidae. Cockroaches. Blackbeetles. Periplaneta --- Trigoniidae. Anodonta --- Helicidae. Helix --- Ascaridae. Ascaris --- Invertebrates --- Zoomorphology. Zooanatomy --- Veterinary dissection.
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Mammals --- Genomes --- Mice --- Human genetics --- Genome, Human --- Genomic Library --- Mammifères --- Souris --- Génétique humaine --- Genetics --- genetics --- Génétique --- Génomes --- Genomes. --- Human genetics. --- Genome, Human. --- Genomic Library. --- Genetics. --- Genome Library --- Genome Libraries --- Genomic Libraries --- Libraries, Genome --- Libraries, Genomic --- Library, Genome --- Library, Genomic --- Human Genome --- Genomes, Human --- Human Genomes --- House mice --- House mouse --- Mouse --- Mus musculus --- Eutheria --- Mammalia --- Mammalians --- Prototheria --- Theria --- Genetics & Genomics. --- Mammals. --- Mice, Laboratory --- Mouse, House --- Mouse, Laboratory --- Mouse, Swiss --- Mus domesticus --- Mus musculus domesticus --- Swiss Mice --- Mice, House --- Mus --- House Mice --- House Mouse --- Laboratory Mice --- Laboratory Mouse --- Mice, Swiss --- Swiss Mouse --- domesticus, Mus musculus --- Mammal --- Rodents --- Vertebrates --- Genes --- Heredity, Human --- Human biology --- Physical anthropology --- Genomics --- Haploidy --- International Mammalian Genome Society. --- IMGS --- International Mammalian Genome Society
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The generation of genetically modified mice is absolutely crucial to gene function studies today, primarily because mice are genetically similar to man and because gene function studies in mice are in the context of a whole organism, making them particularly useful. In Transgenic Mouse Methods and Protocols, Second Edition, expert research explore current advances in the field through detailed laboratory protocols. Chapters provide a general introduction outlining how to deal with mice and how to generate transgenic mouse models, explore the generation of conditional and induced knockout and transgenic mice, and offer alternative routes to studying gene function in mice. Composed in the highly successful Methods in Molecular Biology™ series format, each chapter contains a brief introduction, step-by-step methods, a list of necessary materials, and a Notes section which shares tips on troubleshooting and avoiding known pitfalls. Comprehensive and state-of-the-art, Transgenic Mouse Methods and Protocols, Second Edition is the ideal guide for all researchers interested in the latest information about the production and analysis of transgenic and knockout mice.
Transgenic mice --- Animals, Genetically Modified --- Investigative Techniques --- Mice --- Analytical, Diagnostic and Therapeutic Techniques and Equipment --- Murinae --- Animal Population Groups --- Animals --- Muridae --- Eukaryota --- Rodentia --- Mammals --- Organisms --- Vertebrates --- Chordata --- Mice, Transgenic --- Genetic Techniques --- Biology --- Health & Biological Sciences --- Genetics --- Genetic Technic --- Genetic Technics --- Genetic Technique --- Technic, Genetic --- Technics, Genetic --- Technique, Genetic --- Techniques, Genetic --- Founder Mice, Transgenic --- Mouse, Founder, Transgenic --- Mouse, Transgenic --- Transgenic Mice --- Mice, Transgenic Founder --- Transgenic Founder Mice --- Transgenic Mouse --- Chordates --- Chordate --- Vertebrate --- Mammalia --- Mammal --- Rodents --- Beavers --- Capybaras --- Castor Beaver --- Dipodidae --- Hydrochaeris --- Jerboas --- Beaver --- Capybara --- Hydrochaeri --- Jerboa --- Rodent --- Rodentias --- Eucarya --- Eukarya --- Eukaryotes --- Eukaryotas --- Eukaryote --- Murids --- Murid --- Animalia --- Animal --- Metazoa --- Animal Population Group --- Population Group, Animal --- Population Groups, Animal --- Acomys --- Apodemus --- Bandicoot Rats --- Bandicota --- Mastomys --- Praomys --- Rats, Bandicoot --- Bandicoot Rat --- Bandicotas --- Rat, Bandicoot --- Mice, Laboratory --- Mouse --- Mouse, House --- Mouse, Laboratory --- Mouse, Swiss --- Mus domesticus --- Mus musculus domesticus --- Swiss Mice --- Mice, House --- Mus --- Mus musculus --- House Mice --- House Mouse --- Laboratory Mice --- Laboratory Mouse --- Mice, Swiss --- Swiss Mouse --- domesticus, Mus musculus --- Investigative Technics --- Investigative Technic --- Investigative Technique --- Technic, Investigative --- Technics, Investigative --- Technique, Investigative --- Techniques, Investigative --- Founder Animals, Transgenic --- GMO Animals --- Genetically Engineered Animals --- Animals, Transgenic --- Genetically Modified Animals --- Transgenic Animals --- Animal, GMO --- Animal, Genetically Engineered --- Animal, Genetically Modified --- Animal, Transgenic --- Animal, Transgenic Founder --- Animals, GMO --- Animals, Genetically Engineered --- Animals, Transgenic Founder --- Engineered Animal, Genetically --- Engineered Animals, Genetically --- Founder Animal, Transgenic --- GMO Animal --- Genetically Engineered Animal --- Genetically Modified Animal --- Modified Animal, Genetically --- Modified Animals, Genetically --- Transgenic Animal --- Transgenic Founder Animal --- Transgenic Founder Animals --- methods --- Animal genetics. --- Genetic engineering. --- Medical genetics. --- Animal Genetics and Genomics. --- Genetic Engineering. --- Gene Function. --- Designed genetic change --- Engineering, Genetic --- Gene splicing --- Genetic intervention --- Genetic surgery --- Genetic recombination --- Biotechnology --- Transgenic organisms --- Clinical genetics --- Diseases --- Heredity of disease --- Human genetics --- Medical sciences --- Pathology --- Genetic disorders --- Genetic aspects --- Transgenic mice - Laboratory manuals
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