An investigation of the role of auditory cortex in sound localization using muscimol‐releasing Elvax

Abstract

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.

Cortico‐cortical connectivity within ferret auditory cortex

“…The multiple inputs to the auditory cortex, and the multiple pathways through the auditory cortex, are possible reasons why the immediate and temporary nature of cortical inactivation via cooling produces such pronounced behavioral deficits when compared with the rather more nuanced changes observed after more prolonged forms of inactivation or permanent lesions (Heffner, 1997; Smith et al, 2004; Bizley et al, 2007b; Malhotra and Lomber, 2007; Nodal et al, 2010, 2012). These multiple pathways potentially provide the auditory cortex with a basis by which considerable compensatory plasticity can occur, with information organized in a frequency‐specific way still gaining access to the auditory cortex even in the absence of an intact auditory core.…”

A Rate Code for Sound Azimuth in Monkey Auditory Cortex: Implications for Human Neuroimaging Studies

“…Although lesions that include auditory cortex can impair sound localization in both animals and humans (Sanchez-Longo and Forster, 1958;Jenkins and Masterton, 1982;Thompson and Cortez, 1983;Hefner and Heffner, 1986;Zatorre and Penhune, 2001;Smith et al, 2004;King et al, 2007), human neuroimaging studies have had mixed success at identifying differential patterns of activation as a function of sound location. For monaural sounds, activation is stronger in the contralateral than in the ipsilateral primary auditory cortex (Woldorff et al, 1999;Petkov et al, 2004;Krumbholz et al, 2005a), but no contralateral preference has been found for more realistic binaural stimuli (Woldorff et al, 1999;Brunetti et al, 2005;Krumbholz et al, 2005b;Zimmer and Macaluso, 2005;Zimmer et al, 2006).…”

Populations of auditory cortical neurons can accurately encode acoustic space across stimulus intensity

“…Unilateral lesions of the auditory cortex have been shown to produce deficits in contralesional space in a variety of species (1)(2)(3)(4), indicating a critical role for auditory cortex. However, despite considerable effort to determine how the cerebral cortex processes acoustic space, our understanding remains rudimentary (e.g., [5][6][7][8][9][10][11][12][13][14][15][16][17].…”