Activity-dependent tuning and the NMDA receptor.

The refinement of the topographic map of visual space within the optic tectum of the frog is activity-dependent. The use of the three-eyed frog preparation to assay the operation of this fine-tuning mechanism indicates that this process is mediated by the NMDA receptor: Chronic in vivo treatment with APV, an NMDA antagonist, disrupts the segregation of retinal afferents into eye-specific zones while NMDA treatment sharpens this pattern. This latter effect is accompanied by a decreased sensitivity of the system to applied NMDA. Activation of the NMDA receptor may mediate the fine-tuning mechanism by initiating the stabilization of appropriate synapses. The requirements for NMDA receptor activation necessitate the convergence of terminals carrying correlated activity patterns. Such patterns of activity are provided by ganglion cells whose cell bodies lie near one another in the retina, and who should therefore, in an accurate visual map, terminate near one another in the tectum. Synapses from ganglion cells who do not neighbor one another in the retina have uncorrelated firing patterns and therefore do not activate the NMDA receptor. These synapses then would not be stabilized relative to one another. In addition to organizing the retinal projection, NMDA receptor activation may also modulate retinal ganglion cell arbor morphology, since chronic in vivo APV or NMDA treatments decrease arbor density. These results are discussed in terms of the effect of NMDA receptor activation on branch initiation and the rate of branch retraction.