NMDA-receptor antagonists disrupt the formation of the auditory space map in the mammalian superior colliculus

In the ferret (Mustela putorius) the map of auditory space in the deeper layers of the superior colliculus (SC) matures over a period of several postnatal weeks, a process known to be guided by both visual and auditory experience. The auditory responses are initially very broadly tuned, and gradually become more selective for specific sound locations that coincide with the visual receptive fields recorded in the same region of the SC. To investigate the possible involvement of NMDA-type glutamate receptors in the postnatal development of this auditory representation, we have reared ferrets in which 400 μm thick sheets of the slow-release polymer Elvax, containing the NMDA receptor antagonists MK801 or APV, were placed on the dorsal surface of the SC. The Elvax was implanted on postnatal day (P) 25-27, just before the onset of hearing, and removed 5-6 weeks later, just prior to recording from the SC on around P61-70. In vitro measurements with Elvax containing ³H-MK801 revealed that the amount of drug released declined sharply over the first 10 d and then stabilized at a fairly constant rate for the following 5 weeks. These in vitro data were found to parallel the in vivo release of MK801 from implanted Elvax slices. Diffusion of MK801 from the implant was measured and significant levels were found within 800 μm of the SC surface, suggesting that the action of MK801 was restricted to the superficial and intermediate layers of the nucleus.
Extracellular recordings were made from visual and auditory units in the SC in response to free-field stimulation. The visual responses of units recorded in the superficial layers appeared to be unaffected by either of the drug treatments, and formed a normal, adult- like map of visual azimuth along the rostrocaudal axis of the SC in all animals. Most of the auditory single-unit responses recorded at this age in normal, unoperated controls were spatially tuned and topographically organized, although the map of sound azimuth was less precise than that in adult ferrets. Data from age-matched control animals that had been reared with drug-free Elvax implants were not statistically different from the unoperated juvenile ferrets. However, in animals reared with APV or MK801 Elvax implants, there was an increase in the relative numbers of auditory units that were ambiguously tuned to two or more locations. In the MK801 group, the proportion of units tuned to a single location in space was significantly reduced compared to either of the juvenile control groups. The topography of the auditory representation was also severely impaired in animals treated with either MK801 or APV during this period of development, resulting in a much poorer alignment with the visual representation.
Adult animals that had received MK801 Elvax implants for the same duration, but beginning at P108-115, also showed a significant reduction in the proportion of tuned auditory units compared to age-matched, drug-free controls. However, in contrast to the juvenile ferrets, the topographic variation in azimuthal selectivity within the SC appeared to be unaffected by NMDA-receptor blockade in the adult animals.
These data suggest that NMDA receptors play a critical role in the activity-dependent process by which a map of auditory space in the SC is elaborated during development. 
© 1995 by Society for Neuroscience