Lesion studies suggest that primary auditory cortex (A1) is required for accurate sound localization by carnivores and primates. In order to elucidate further its role in spatial hearing, we examined the behavioural consequences of reversibly inactivating ferret A1 over long periods, using Elvax implants releasing the GABA(A) receptor agonist muscimol. Sub-dural polymer placements were shown to deliver relatively constant levels of muscimol to underlying cortex for >5 months. The measured diffusion of muscimol beneath and around the implant was limited to 1 mm. Cortical silencing was assessed electrophysiologically in both auditory and visual cortices. This exhibited rapid onset and was reversed within a few hours of implant removal. Inactivation of cortical neurons extended to all layers for implants lasting up to 6 weeks and throughout at least layers I-IV for longer placements, whereas thalamic activity in layer IV appeared to be unaffected. Blockade of cortical neurons in the deeper layers was restricted to < or = 500 microm from the edge of the implant, but was usually more widespread in the superficial layers. In contrast, drug-free Elvax implants had little discernible effect on the responses of the underlying cortical neurons. Bilateral implants of muscimol-Elvax over A1 produced significant deficits in the localization of brief sounds in horizontal space and particularly a reduced ability to discriminate between anterior and posterior sound sources. The performance of these ferrets gradually improved over the period in which the Elvax was in place and attained that of control animals following its removal. Although similar in nature, these deficits were less pronounced than those caused by cortical lesions and suggest a specific role for A1 in resolving the spatial ambiguities inherent in auditory localization cues.

. Effects of altering spectral cues in infancy on horizontal and vertical sound localization by adult ferrets. J. Neurophysiol. 82: 2294Neurophysiol. 82: -2309Neurophysiol. 82: , 1999. We investigated the behavioral consequences of removing the pinna and concha of the external ear bilaterally in infancy on the sound localization ability of adult ferrets. Altering spectral cues in this manner has previously been shown to disrupt the development of the neural representation of auditory space in the superior colliculus. Using broadband noise stimuli, we tested pinnae-removed ferrets and normal ferrets in three sound localization tasks. In each case, we found that both groups of animals performed significantly better when longer duration noise bursts were used. In a relative localization task, we measured the acuity with which the ferrets could discriminate between two speakers in the horizontal plane. The speakers were placed symmetrically either around the anterior midline or around a position 45°lateral to the midline. In this task, the pinnae-removed ferrets achieved very similar scores to the normal ferrets. By contrast, in another relative localization task that measured localization ability in the midsagittal plane, pinnae-removed ferrets performed less well than normals. In an absolute localization task, 12 speakers were spaced at 30°intervals in the horizontal plane at the level of the ferrets' ears. Overall, the pinnae-removed ferrets also performed poorly in this task compared with normal ferrets: they made significantly fewer correct responses, larger localization errors and more front-back errors. Both normal and pinnae-removed animals showed an improvement in performance with practice, although the pattern of improvement differed for each group. The largest improvements in localization accuracy were achieved by the pinnae-removed ferrets, particularly at the frontal positions, and their performance eventually approached that of the normal animals. Nevertheless, some intergroup differences were still present. In particular, the pinnaeremoved ferrets continued to make significantly more front-back errors than the normals. These deficits can be attributed to differences in the spectral localization cues available to the animals. Acoustical measurements showed that, compared with normal animals, the headrelated transfer functions in the horizontal plane were largely ambiguous around the interaural axis and also contained fewer locationdependent features in the midsagittal plane.