Reversible inactivation of ferret auditory cortex impairs spatial and non-spatial hearing

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 non-spatial hearing by reversibly inactivating the middle ectosylvian gyrus during behavior using cooling (n=2 females) or optogenetics (n=1 female). Optogenetic experiments utilized the mDLx promoter to express Channelrhodopsin2 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 co-located noise. Ferrets implanted with cooling loops were tested in additional conditions that revealed no deficits for 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 non-spatial 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 non- spatial 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.