title: Bidirectional Regulation of Innate and Learned Behaviors That Rely on Frequency Discrimination by Cortical Inhibitory Neurons.
abstract: The ability to discriminate tones of different frequencies is fundamentally important for everyday hearing. While neurons in the primary auditory cortex (AC) respond differentially to tones of different frequencies, whether and how AC regulates auditory behaviors that rely on frequency discrimination remains poorly understood. Here, we find that the level of activity of inhibitory neurons in AC controls frequency specificity in innate and learned auditory behaviors that rely on frequency discrimination. Photoactivation of parvalbumin-positive interneurons (PVs) improved the ability of the mouse to detect a shift in tone frequency, whereas photosuppression of PVs impaired the performance. Furthermore, photosuppression of PVs during discriminative auditory fear conditioning increased generalization of conditioned response across tone frequencies, whereas PV photoactivation preserved normal specificity of learning. The observed changes in behavioral performance were correlated with bidirectional changes in the magnitude of tone-evoked responses, consistent with predictions of a model of a coupled excitatory-inhibitory cortical network. Direct photoactivation of excitatory neurons, which did not change tone-evoked response magnitude, did not affect behavioral performance in either task. Our results identify a new function for inhibition in the auditory cortex, demonstrating that it can improve or impair acuity of innate and learned auditory behaviors that rely on frequency discrimination.
authors.affiliation: Department of Otorhinolaryngology HNS, Neuroscience Graduate Group, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Mark
authors.initials: M
authors.lastname: Aizenberg
authors.affiliation: Department of Otorhinolaryngology HNS, Neuroscience Graduate Group, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Mwilambwe-Tshilobo
authors.affiliation: Physics Graduate Group, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: John J
authors.initials: JJ
authors.lastname: Briguglio
authors.affiliation: Department of Otorhinolaryngology HNS, Neuroscience Graduate Group, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Ryan G
authors.initials: RG
authors.lastname: Natan
authors.affiliation: Department of Otorhinolaryngology HNS, Neuroscience Graduate Group, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Maria N
authors.initials: MN
authors.lastname: Geffen
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001303:Auditory Cortex / Q000502:physiology* / Q000528:radiation effects; D001522:Behavior, Animal / Q000528:radiation effects; D015415:Biomarkers / Q000378:metabolism; D003214:Conditioning, Classical; D003216:Conditioning, Operant; D004193:Discrimination Learning / Q000528:radiation effects; D005794:Generalization, Response / Q000528:radiation effects; D007323:Instinct; D007395:Interneurons / Q000502:physiology* / Q000528:radiation effects; D008027:Light; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010320:Parvalbumins / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: D015415:Biomarkers; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D010320:Parvalbumins; D011993:Recombinant Fusion Proteins