Suppression of cortical NMDA receptor function prevents development of orientation selectivity in the primary visual cortex.

Selectivity to visual stimulus orientation is a basic cortical functional property believed to be crucial for normal vision. Maturation of this neuronal property requires neural activity. Still, it is unclear what might be the molecular basis for such activity-dependent processes and whether activity has an instructive or permissive role in development of orientation selectivity. There is strong evidence that the NMDA subtype of the glutamate receptor regulates activity-dependent mechanisms of ocular dominance plasticity during cortical development. For this reason, we have hypothesized that the NMDA receptor participates in activity-dependent mechanisms that sculpt orientation selectivity of cortical neurons. We used chronic in vivo infusion of antisense oligodeoxynucleotides (ODNs) to suppress NMDA receptor function in primary visual cortex during the period when orientation selectivity develops in ferrets. Chronic suppression of NMDA receptor function prevented the development of orientation and stimulus size selectivity in most cortical cells tested. In contrast, treatment with control sense or missense ODNs did not affect development of orientation selectivity, indicating specificity of effects. Importantly, antisense ODN treatment did not impair visually driven activity, which is required for development to occur. Moreover, orientation selectivity of cortical cells was not disrupted by antisense ODN treatment in mature animals, indicating developmental relevance of the effects. In conclusion, our findings document for the first time that cortical NMDA receptors are essential for the maturation of orientation selectivity. This result supports the notion that activity has an instructive role in sculpting the connections that underlie orientation selectivity in visual cortex.