Reversible Inactivation of Ferret Auditory Cortex Impairs Spatial and Nonspatial Hearing. 2023

Stephen M Town, and Katarina C Poole, and Katherine C Wood, and Jennifer K Bizley
Ear Institute, University College London, London, WC1X 8EE, United Kingdom s.town@ucl.ac.uk j.bizley@ucl.ac.uk.

A key question in auditory neuroscience is to what extent are brain regions functionally specialized for processing specific sound features, such as location and identity. In auditory cortex, correlations between neural activity and sounds support both the specialization of distinct cortical subfields, and encoding of multiple sound features within individual cortical areas. However, few studies have tested the contribution of auditory cortex to hearing in multiple contexts. Here we determined the role of ferret primary auditory cortex in both spatial and nonspatial hearing by reversibly inactivating the middle ectosylvian gyrus during behavior using cooling (n = 2 females) or optogenetics (n = 1 female). Optogenetic experiments used the mDLx promoter to express Channelrhodopsin-2 in GABAergic interneurons, and we confirmed both viral expression (n = 2 females) and light-driven suppression of spiking activity in auditory cortex, recorded using Neuropixels under anesthesia (n = 465 units from 2 additional untrained female ferrets). Cortical inactivation via cooling or optogenetics impaired vowel discrimination in colocated noise. Ferrets implanted with cooling loops were tested in additional conditions that revealed no deficit when identifying vowels in clean conditions, or when the temporally coincident vowel and noise were spatially separated by 180 degrees. These animals did, however, show impaired sound localization when inactivating the same auditory cortical region implicated in vowel discrimination in noise. Our results demonstrate that, as a brain region showing mixed selectivity for spatial and nonspatial features of sound, primary auditory cortex contributes to multiple forms of hearing.SIGNIFICANCE STATEMENT Neurons in primary auditory cortex are often sensitive to the location and identity of sounds. Here we inactivated auditory cortex during spatial and nonspatial listening tasks using cooling, or optogenetics. Auditory cortical inactivation impaired multiple behaviors, demonstrating a role in both the analysis of sound location and identity and confirming a functional contribution of mixed selectivity observed in neural activity. Parallel optogenetic experiments in two additional untrained ferrets linked behavior to physiology by demonstrating that expression of Channelrhodopsin-2 permitted rapid light-driven suppression of auditory cortical activity recorded under anesthesia.

UI MeSH Term Description Entries
D005260 Female Females
D005289 Ferrets Semidomesticated variety of European polecat much used for hunting RODENTS and/or RABBITS and as a laboratory animal. It is in the subfamily Mustelinae, family MUSTELIDAE. Domestic Polecat,Domestic Polecats,European Polecat,European Polecats,Ferret,Mustela putorius,Mustela putorius furo,Polecat, Domestic,Polecat, European,Polecats, Domestic,Polecats, European
D006309 Hearing The ability or act of sensing and transducing ACOUSTIC STIMULATION to the CENTRAL NERVOUS SYSTEM. It is also called audition. Audition
D000075402 Channelrhodopsins A subfamily of rhodopsin proteins that function as light-gated ion channels in GREEN ALGAE. Channelrhodopsin
D000161 Acoustic Stimulation Use of sound to elicit a response in the nervous system. Auditory Stimulation,Stimulation, Acoustic,Stimulation, Auditory
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001303 Auditory Cortex The region of the cerebral cortex that receives the auditory radiation from the MEDIAL GENICULATE BODY. Brodmann Area 41,Brodmann Area 42,Brodmann's Area 41,Heschl Gyrus,Heschl's Gyrus,Auditory Area,Heschl's Convolutions,Heschl's Gyri,Primary Auditory Cortex,Temporal Auditory Area,Transverse Temporal Gyri,Area 41, Brodmann,Area 41, Brodmann's,Area 42, Brodmann,Area, Auditory,Area, Temporal Auditory,Auditory Areas,Auditory Cortex, Primary,Brodmanns Area 41,Cortex, Auditory,Cortex, Primary Auditory,Gyrus, Heschl,Gyrus, Heschl's,Gyrus, Transverse Temporal,Heschl Convolutions,Heschl Gyri,Heschls Convolutions,Heschls Gyri,Heschls Gyrus,Primary Auditory Cortices,Temporal Auditory Areas,Temporal Gyrus, Transverse,Transverse Temporal Gyrus
D001307 Auditory Perception The process whereby auditory stimuli are selected, organized, and interpreted by the organism. Auditory Processing,Perception, Auditory,Processing, Auditory
D013017 Sound Localization Ability to determine the specific location of a sound source. Auditory Localization,Auditory Localizations,Localization, Auditory,Localization, Sound,Localizations, Auditory,Localizations, Sound,Sound Localizations

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