Adenovirus-mediated NMDA receptor knockouts in the rat hippocampal CA1 region.

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.