Abstract
Adenoviral antisense constructs of the rat N-methyl-D-aspartate (NMDA) receptor subunit 1 (R1) were assessed for creating NMDAR1 knockouts in rat hippocampal CA1 regions in vivo. In situ hybridization analyses showed that virus-derived antisense transcripts were detected up to 5 weeks postinfection (p.i.). Although immunological methods failed to demonstrate a reduction of NMDA receptor protein, whole-cell recording showed that neurons in the transduced regions were deficient in NMDA receptor-mediated synaptic currents, but not alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor (AMPAR)-mediated synaptic currents. Thus, the data suggest that adenovirus technology can be used to locally knockout specific gene function for dissecting molecular mechanisms of synaptic plasticity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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2-Amino-5-phosphonovalerate / pharmacology
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6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
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Adenoviridae
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Amino Acid Sequence
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Animals
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Hippocampus / physiology*
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Immunohistochemistry
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In Situ Hybridization
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Membrane Potentials / drug effects
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Molecular Sequence Data
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Peptide Fragments / chemistry
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Peptide Fragments / immunology
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Pyramidal Cells / physiology*
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RNA, Antisense / biosynthesis*
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Rats
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Rats, Mutant Strains
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Receptors, AMPA / physiology
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Receptors, N-Methyl-D-Aspartate / biosynthesis
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Receptors, N-Methyl-D-Aspartate / deficiency*
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Receptors, N-Methyl-D-Aspartate / genetics*
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Synapses / physiology*
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Transcription, Genetic
Substances
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NMDA receptor A1
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Peptide Fragments
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RNA, Antisense
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Receptors, AMPA
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Receptors, N-Methyl-D-Aspartate
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6-Cyano-7-nitroquinoxaline-2,3-dione
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2-Amino-5-phosphonovalerate