title: 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.
authors.affiliation: Nature Reviews Drug Discovery, 4 Crinan Street, London N1 9XW, UK.
authors.forename: Adam L
authors.initials: AL
authors.lastname: Smith
authors.forename: Carl H
authors.initials: CH
authors.lastname: Parsons
authors.forename: Richard G
authors.initials: RG
authors.lastname: Lanyon
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Bizley
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Akerman
authors.forename: Gary E
authors.initials: GE
authors.lastname: Baker
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Dempster
authors.forename: Ian D
authors.initials: ID
authors.lastname: Thompson
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: King
mesh_terms: D000161:Acoustic Stimulation; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001303:Auditory Cortex / Q000187:drug effects* / Q000502:physiology; D001522:Behavior, Animal; D001931:Brain Mapping; D004594:Electrophysiology; D005289:Ferrets; D007839:Functional Laterality; D018755:GABA Agonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D015918:Infusion Pumps, Implantable; D009118:Muscimol / Q000494:pharmacology*; D010775:Photic Stimulation; D010897:Pitch Discrimination; D011145:Polyvinyls / Q000008:administration & dosage*; D013017:Sound Localization / Q000187:drug effects*; D013997:Time Factors; D014018:Tissue Distribution; D014793:Visual Cortex / Q000187:drug effects / Q000502:physiology
chemical_list: D018755:GABA Agonists; D011145:Polyvinyls; C016438:ethylenevinylacetate copolymer; D009118:Muscimol