Supression of the NR1 subunit of the nmda receptor using antisense techniques: Effects on synaptic transmission and visual function

Purpose. Previous studies of NMDA receptor function in visual plasticity have employed pharmacologie blockers of NMDA receptors. The results of such experiments have been confounded by nonspecific effects on visual function such as loss of orientation selectivity and reduction of visual responses. To obtain more specific supression effects on NMDA receptors we have used antisense oligodeoxynucleotides (ODNs) targeted to the NR1 subunit. Methods. Sense and antisense ODNs targeted to the 5' end of the NR1 subunit mRNA were infused into the primary visual cortex of young ferrets. Immunohistochemistry and western blot analysis were performed on cortical tissue after ODN treatment in order to confirm that NR1 subunit expression was decreased. Patch clamp recordings were conducted in in vitro cortical slice preparations to examine effects of ODN application on synaptic transmission. Recordings in vivo were made to determine the visual response properties of cortical cells after ODN treatment. Results. Antisense, but not sense, ODNs significantly decreased expression of the NR1 subunit and concommitantly reduced NMDA receptor mediated synaptic currents in cortical neurons. Direction selectivity, orientation selectivity, and responsiveness to visual stimuli were preserved in both sense and antisense ODN treated neurons. Contusions. Decreasing NR1 subunit expression in primary visual cortex using antisense ODNs is an effective way to decrease NMDA receptor mediated synaptic transmission. This result indicates that the NR1 subunit is required for NMDA receptor-mediated synaptic transmission in visual cortex. This treatment is selective and does not affect visual function.