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  • 1
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    Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-08-09
    Description: Various chronic antidepressant treatments increase adult hippocampal neurogenesis, but the functional importance of this phenomenon remains unclear. Here, using genetic and radiological methods, we show that disrupting antidepressant-induced neurogenesis blocks behavioral responses to antidepressants. Serotonin 1A receptor null mice were insensitive to the neurogenic and behavioral effects of fluoxetine, a serotonin selective reuptake inhibitor. X-irradiation of a restricted region of mouse brain containing the hippocampus prevented the neurogenic and behavioral effects of two classes of antidepressants. These findings suggest that the behavioral effects of chronic antidepressants may be mediated by the stimulation of neurogenesis in the hippocampus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Santarelli, Luca -- Saxe, Michael -- Gross, Cornelius -- Surget, Alexandre -- Battaglia, Fortunato -- Dulawa, Stephanie -- Weisstaub, Noelia -- Lee, James -- Duman, Ronald -- Arancio, Ottavio -- Belzung, Catherine -- Hen, Rene -- New York, N.Y. -- Science. 2003 Aug 8;301(5634):805-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Neurobiology and Behavior, Columbia University, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12907793" target="_blank"〉PubMed〈/a〉
    Keywords: 8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology ; Animals ; Antidepressive Agents/*pharmacology ; Antidepressive Agents, Second-Generation/pharmacology ; Antidepressive Agents, Tricyclic/pharmacology ; Behavior, Animal/*drug effects ; Cell Division/drug effects/radiation effects ; Conditioning (Psychology) ; Dentate Gyrus/cytology/drug effects/physiology ; Fear ; Feeding Behavior/drug effects ; Fluoxetine/*pharmacology ; Grooming/drug effects ; Hippocampus/cytology/drug effects/*physiology/radiation effects ; Long-Term Potentiation/radiation effects ; Male ; Mice ; Mice, Knockout ; Neurons/drug effects/*physiology ; Receptors, Serotonin/genetics/metabolism ; Receptors, Serotonin, 5-HT1 ; Stress, Physiological/drug therapy/physiopathology ; Synaptic Transmission/radiation effects
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
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    Modification of ocular defects in mouse developmental glaucoma models by tyrosinase (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-03-08
    Description: Mutations in the cytochrome P450 family 1, subfamily B, polypeptide 1 (CYP1B1) gene are a common cause of human primary congenital glaucoma (PCG). Here we show that Cyp1b1-/- mice have ocular drainage structure abnormalities resembling those reported in human PCG patients. Using Cyp1b1-/- mice, we identified the tyrosinase gene (Tyr) as a modifier of the drainage structure phenotype, with Tyr deficiency increasing the magnitude of dysgenesis. The severe dysgenesis in eyes lacking both CYP1B1 and TYR was alleviated by administration of the tyrosinase product dihydroxyphenylalanine (l-dopa). Tyr also modified the drainage structure dysgenesis in mice with a mutant Foxc1 gene, which is also involved in PCG. These experiments raise the possibility that a tyrosinase/l-dopa pathway modifies human PCG, which could open new therapeutic avenues.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Libby, Richard T -- Smith, Richard S -- Savinova, Olga V -- Zabaleta, Adriana -- Martin, Janice E -- Gonzalez, Frank J -- John, Simon W M -- CA34196/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2003 Mar 7;299(5612):1578-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Jackson Laboratory, Bar Harbor, ME 04609, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12624268" target="_blank"〉PubMed〈/a〉
    Keywords: Albinism, Ocular/genetics/pathology ; Animals ; Anterior Eye Segment/*abnormalities ; Aryl Hydrocarbon Hydroxylases/deficiency/genetics ; Cornea/abnormalities ; Cytochrome P-450 CYP1B1 ; *DNA-Binding Proteins ; Disease Models, Animal ; Female ; Forkhead Transcription Factors ; Glaucoma/*congenital/enzymology/*genetics/pathology ; Intraocular Pressure ; Iris/abnormalities ; Levodopa/administration & dosage/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Monophenol Monooxygenase/deficiency/*genetics/metabolism ; Mutation ; Phenotype ; Pregnancy ; Trabecular Meshwork/abnormalities ; Transcription Factors/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    Generation of viable cholesterol-free mice (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-12-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wechsler, A -- Brafman, A -- Shafir, M -- Heverin, M -- Gottlieb, H -- Damari, G -- Gozlan-Kelner, S -- Spivak, I -- Moshkin, O -- Fridman, E -- Becker, Y -- Skaliter, R -- Einat, P -- Faerman, A -- Bjorkhem, I -- Feinstein, E -- New York, N.Y. -- Science. 2003 Dec 19;302(5653):2087.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Quark Biotech, Inc., 10265 Carnegie Avenue, Cleveland, OH 44106, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14684813" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue ; Animals ; Bile Acids and Salts/biosynthesis ; Cholesterol/blood/*deficiency/metabolism/*physiology ; Desmosterol/*metabolism ; Female ; Gene Targeting ; Growth ; Humans ; Infertility ; Liver/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Models, Animal ; Nerve Tissue Proteins/*genetics/metabolism ; Oxidoreductases Acting on CH-CH Group Donors/*genetics/metabolism ; Phenotype ; Sex Characteristics ; Testis/pathology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-02-08
    Description: Nitric oxide was found to trigger mitochondrial biogenesis in cells as diverse as brown adipocytes and 3T3-L1, U937, and HeLa cells. This effect of nitric oxide was dependent on guanosine 3',5'-monophosphate (cGMP) and was mediated by the induction of peroxisome proliferator-activated receptor gamma coactivator 1alpha, a master regulator of mitochondrial biogenesis. Moreover, the mitochondrial biogenesis induced by exposure to cold was markedly reduced in brown adipose tissue of endothelial nitric oxide synthase null-mutant (eNOS-/-) mice, which had a reduced metabolic rate and accelerated weight gain as compared to wild-type mice. Thus, a nitric oxide-cGMP-dependent pathway controls mitochondrial biogenesis and body energy balance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nisoli, Enzo -- Clementi, Emilio -- Paolucci, Clara -- Cozzi, Valeria -- Tonello, Cristina -- Sciorati, Clara -- Bracale, Renata -- Valerio, Alessandra -- Francolini, Maura -- Moncada, Salvador -- Carruba, Michele O -- New York, N.Y. -- Science. 2003 Feb 7;299(5608):896-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Preclinical Sciences, Center for Study and Research on Obesity, Luigi Sacco Hospital, University of Milan, Milan 20157, Italy. enzo.nisoli@unimi.it〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12574632" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; 8-Bromo Cyclic Adenosine Monophosphate/pharmacology ; Adipocytes/*metabolism/ultrastructure ; Adipose Tissue, Brown/cytology/metabolism/ultrastructure ; Animals ; Cold Temperature ; Cyclic GMP/metabolism ; DNA, Mitochondrial/metabolism ; DNA-Binding Proteins/metabolism ; Eating ; Energy Metabolism ; Female ; HeLa Cells ; High Mobility Group Proteins ; Humans ; Male ; Mice ; Mice, Knockout ; Mitochondria/*metabolism/ultrastructure ; *Mitochondrial Proteins ; Motor Activity ; NF-E2-Related Factor 1 ; Nitric Oxide/*physiology ; Nitric Oxide Synthase/genetics/*metabolism ; Nitric Oxide Synthase Type II ; Nitric Oxide Synthase Type III ; Nuclear Proteins/metabolism ; Nuclear Respiratory Factors ; Oligonucleotides, Antisense/pharmacology ; Oxadiazoles/pharmacology ; Oxygen Consumption ; Penicillamine/*analogs & derivatives/pharmacology ; Quinoxalines/pharmacology ; RNA, Messenger/genetics/metabolism ; Rats ; Signal Transduction ; Trans-Activators/metabolism ; Transcription Factors/metabolism ; U937 Cells ; Weight Gain
    Print ISSN: 0036-8075
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  • 5
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    Evidence for selective advantage of pathogenic FGFR2 mutations in the male germ line (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-08-02
    Description: Observed mutation rates in humans appear higher in male than female gametes and often increase with paternal age. This bias, usually attributed to the accumulation of replication errors or inefficient repair processes, has been difficult to study directly. Here, we describe a sensitive method to quantify substitutions at nucleotide 755 of the fibroblast growth factor receptor 2 (FGFR2) gene in sperm. Although substitution levels increase with age, we show that even high levels originate from infrequent mutational events. We propose that these FGFR2 mutations, although harmful to embryonic development, are paradoxically enriched because they confer a selective advantage to the spermatogonial cells in which they arise.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goriely, Anne -- McVean, Gilean A T -- Rojmyr, Maria -- Ingemarsson, Bjorn -- Wilkie, Andrew O M -- New York, N.Y. -- Science. 2003 Aug 1;301(5633):643-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12893942" target="_blank"〉PubMed〈/a〉
    Keywords: Acrocephalosyndactylia/*genetics ; Adult ; Aged ; Aging ; Amino Acid Substitution ; DNA Mutational Analysis ; Female ; Heterozygote ; Humans ; Ligands ; Male ; Middle Aged ; Models, Genetic ; Models, Statistical ; *Mutation ; *Paternal Age ; Point Mutation ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Receptor Protein-Tyrosine Kinases/chemistry/*genetics/metabolism ; Receptor, Fibroblast Growth Factor, Type 2 ; Receptors, Fibroblast Growth Factor/chemistry/*genetics/metabolism ; *Selection, Genetic ; Sequence Analysis, DNA ; Sex Characteristics ; Spermatogenesis ; Spermatogonia/*physiology ; Spermatozoa/physiology ; Stem Cells/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
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  • 6
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    Retraction in amoeboid cell motility powered by cytoskeletal dynamics (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-11-25
    Description: Cells crawl by coupling protrusion of their leading edge with retraction of their cell body. Protrusion is generated by the polymerization and bundling of filaments, but the mechanism of retraction is less clear. We have reconstituted retraction in vitro by adding Yersinia tyrosine phosphatase to the major sperm protein-based motility apparatus assembled from Ascaris sperm extracts. Retraction in vitro parallels that observed in vivo and is generated primarily by disassembly and rearrangement of the cytoskeleton. Therefore, cytoskeletal dynamics alone, unassisted by conventional motors, are able to generate both of these central components of amoeboid locomotion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miao, Long -- Vanderlinde, Orion -- Stewart, Murray -- Roberts, Thomas M -- R37GM29994/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2003 Nov 21;302(5649):1405-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14631043" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/physiology ; Adenosine Triphosphate/metabolism/pharmacology ; Animals ; Ascaris suum/*cytology/physiology ; Biopolymers ; Cell Adhesion ; Cell Extracts ; Cell Movement/*physiology ; Cytoplasmic Vesicles/physiology ; Cytoskeleton/*physiology ; Helminth Proteins/chemistry/metabolism/*physiology ; Hydrogen-Ion Concentration ; Male ; Myosins/physiology ; Phosphorylation ; Protein Tyrosine Phosphatases/metabolism ; Pseudopodia/physiology ; Spermatozoa/physiology/ultrastructure ; Yersinia enterocolitica/enzymology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
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  • 7
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    CB1 cannabinoid receptors and on-demand defense against excitotoxicity (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-10-04
    Description: Abnormally high spiking activity can damage neurons. Signaling systems to protect neurons from the consequences of abnormal discharge activity have been postulated. We generated conditional mutant mice that lack expression of the cannabinoid receptor type 1 in principal forebrain neurons but not in adjacent inhibitory interneurons. In mutant mice,the excitotoxin kainic acid (KA) induced excessive seizures in vivo. The threshold to KA-induced neuronal excitation in vitro was severely reduced in hippocampal pyramidal neurons of mutants. KA administration rapidly raised hippocampal levels of anandamide and induced protective mechanisms in wild-type principal hippocampal neurons. These protective mechanisms could not be triggered in mutant mice. The endogenous cannabinoid system thus provides on-demand protection against acute excitotoxicity in central nervous system neurons.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marsicano, Giovanni -- Goodenough, Sharon -- Monory, Krisztina -- Hermann, Heike -- Eder, Matthias -- Cannich, Astrid -- Azad, Shahnaz C -- Cascio, Maria Grazia -- Gutierrez, Silvia Ortega -- van der Stelt, Mario -- Lopez-Rodriguez, Maria Luz -- Casanova, Emilio -- Schutz, Gunther -- Zieglgansberger, Walter -- Di Marzo, Vincenzo -- Behl, Christian -- Lutz, Beat -- New York, N.Y. -- Science. 2003 Oct 3;302(5642):84-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Genetics of Behaviour, Max-Planck-Institute of Psychiatry, Kraepelinstrabetae 2-10, 80804 Munich, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14526074" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arachidonic Acids/*metabolism/pharmacology ; Brain/drug effects/*metabolism ; Brain-Derived Neurotrophic Factor/genetics/metabolism ; Cannabinoids/*metabolism ; Endocannabinoids ; Epilepsy/*metabolism/physiopathology ; Excitatory Amino Acid Agonists/pharmacology ; Excitatory Postsynaptic Potentials ; Furans/pharmacology ; Gene Expression Regulation/drug effects ; Genes, Immediate-Early ; Glutamic Acid/metabolism ; Glycerides/metabolism ; Hippocampus/drug effects/metabolism ; In Vitro Techniques ; Kainic Acid/pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Mitogen-Activated Protein Kinases/metabolism ; Mutation ; Neurons/drug effects/*metabolism/physiology ; Neuroprotective Agents/metabolism ; Piperidines/pharmacology ; Polyunsaturated Alkamides ; Prosencephalon/drug effects/metabolism ; Pyrazoles/pharmacology ; Receptors, Cannabinoid ; Receptors, Drug/antagonists & inhibitors/genetics/*metabolism ; Signal Transduction ; gamma-Aminobutyric Acid/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
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  • 8
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    Cyclic dynamics in a simple vertebrate predator-prey community (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-11-01
    Description: The collared lemming in the high-Arctic tundra in Greenland is preyed upon by four species of predators that show marked differences in the numbers of lemmings each consumes and in the dependence of their dynamics on lemming density. A predator prey model based on the field-estimated predator responses robustly predicts 4-year periodicity in lemming dynamics, in agreement with long-term empirical data. There is no indication in the field that food or space limits lemming population growth, nor is there need in the model to consider those factors. The cyclic dynamics are driven by a 1-year delay in the numerical response of the stoat and stabilized by strongly density-dependent predation by the arctic fox, the snowy owl, and the long-tailed skua.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gilg, Olivier -- Hanski, Ilkka -- Sittler, Benoit -- New York, N.Y. -- Science. 2003 Oct 31;302(5646):866-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Systematics, Division of Population Biology, Post Office Box 65, 00014 University of Helsinki, Finland. olivier.gilg@libertysurf.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14593179" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arvicolinae/growth & development/*physiology ; Birds/*physiology ; Carnivora/*physiology ; *Ecosystem ; Female ; Foxes/physiology ; Greenland ; Male ; Models, Biological ; Population Density ; Population Dynamics ; *Predatory Behavior ; Seasons ; Strigiformes/physiology
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
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    Amygdalar and hippocampal theta rhythm synchronization during fear memory retrieval (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-08-09
    Description: The amygdalohippocampal circuit plays a pivotal role in Pavlovian fear memory. We simultaneously recorded electrical activity in the lateral amygdala (LA) and the CA1 area of the hippocampus in freely behaving fear-conditioned mice. Patterns of activity were related to fear behavior evoked by conditioned and indifferent sensory stimuli and contexts. Rhythmically synchronized activity at theta frequencies increased between the LA and the CA1 after fear conditioning and became significant during confrontation with conditioned fear stimuli and expression of freezing behavior. Synchronization of theta activities in the amygdalohippocampal network represents a neuronal correlate of conditioned fear, apt to improve neuronal communication during memory retrieval.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Seidenbecher, Thomas -- Laxmi, T Rao -- Stork, Oliver -- Pape, Hans-Christian -- New York, N.Y. -- Science. 2003 Aug 8;301(5634):846-50.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Physiologie, Otto-von-Guericke-Universitat, Leipziger Strasse 44, Magdeburg D-39120, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12907806" target="_blank"〉PubMed〈/a〉
    Keywords: Amygdala/*physiology ; Animals ; Behavior, Animal ; Conditioning (Psychology) ; Cues ; Electrophysiology ; Electroshock ; *Fear ; Hippocampus/*physiology ; Male ; *Memory ; Mice ; Mice, Inbred C57BL ; Motor Activity ; *Theta Rhythm
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
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    Role of subplate neurons in functional maturation of visual cortical columns (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-07-26
    Description: The subplate forms a transient circuit required for development of connections between the thalamus and the cerebral cortex. When subplate neurons are ablated, ocular dominance columns do not form in the visual cortex despite the robust presence of thalamic axons in layer 4. We show that subplate ablation also prevents formation of orientation columns. Visual responses are weak and poorly tuned to orientation. Furthermore, thalamocortical synaptic transmission fails to strengthen, whereas intracortical synapses are unaffected. Thus, subplate circuits are essential not only for the anatomical segregation of thalamic inputs but also for key steps in synaptic remodeling and maturation needed to establish the functional architecture of visual cortex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kanold, Patrick O -- Kara, Prakash -- Reid, R Clay -- Shatz, Carla J -- F32 EY013526/EY/NEI NIH HHS/ -- F32 EY013526-01/EY/NEI NIH HHS/ -- F32 EY1352/EY/NEI NIH HHS/ -- P30 EY12196/EY/NEI NIH HHS/ -- R01 EY02858/EY/NEI NIH HHS/ -- R01 EY10115/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 2003 Jul 25;301(5632):521-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12881571" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons ; Brain-Derived Neurotrophic Factor/pharmacology ; Cats ; Dominance, Ocular ; Electric Stimulation ; Evoked Potentials, Visual ; Excitatory Postsynaptic Potentials ; Female ; Geniculate Bodies/physiology ; Immunotoxins/pharmacology ; Kainic Acid/pharmacology ; Male ; Microelectrodes ; Neurons/*physiology ; Patch-Clamp Techniques ; Receptors, AMPA/genetics/metabolism ; Synapses ; *Synaptic Transmission ; Thalamus/*physiology ; Vision, Ocular ; Visual Cortex/cytology/growth & development/*physiology ; *Visual Pathways
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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