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 microns 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 microns 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.(ABSTRACT TRUNCATED AT 400 WORDS)