NMDA-RECEPTOR ANTAGONISTS DISRUPT THE FORMATION OF THE AUDITORY SPACEMAP IN THE MAMMALIAN SUPERIOR COLLICULUS

In the ferret (Mustela putorius) the map of auditory space in the deep er layers of the superior colliculus (SC) matures over a period of sev eral 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 locatio ns that coincide with the visual receptive fields recorded in the same region of the SC. To investigate the possible involvement of NMDA-typ e glutamate receptors in the postnatal development of this auditory re presentation, we have reared ferrets in which 400 mu m thick sheets of the slow-release polymer Elvax, containing the NMDA receptor antagoni sts MK801 or APV, were placed on the dorsal surface of the SC. The Elv ax 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 H-3- 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 f ollowing 5 weeks. These in vitro data were found to parallel the in vi vo release of MK801 from implanted Elvax slices. Diffusion of MK801 fr om the implant was measured and significant levels were found within 8 00 mu m of the SC surface, suggesting that the action of MK801 was res tricted to the superficial and intermediate layers of the nucleus. Ext racellular recordings were made from visual and auditory units in the SC in response to free-field stimulation. The visual responses of unit s recorded in the superficial layers appeared to be unaffected by eith er of the drug treatments, and formed a normal, adult-like map of visu al 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 adul t ferrets. Data from age-matched control animals that had been reared with drug-free Elvax implants were not statistically different from th e 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 als o 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 Elva x implants for the same duration, but beginning at P108-115, also show ed a significant reduction in the proportion of tuned auditory units c ompared to age-matched, drug-free controls. However, in contrast to th e 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 criti cal role in the activity-dependent process by which a map of auditory space in the SC is elaborated during development.