title: BDNF in Lower Brain Parts Modifies Auditory Fiber Activity to Gain Fidelity but Increases the Risk for Generation of Central Noise After Injury.
abstract: For all sensory organs, the establishment of spatial and temporal cortical resolution is assumed to be initiated by the first sensory experience and a BDNF-dependent increase in intracortical inhibition. To address the potential of cortical BDNF for sound processing, we used mice with a conditional deletion of BDNF in which Cre expression was under the control of the Pax2 or TrkC promoter. BDNF deletion profiles between these mice differ in the organ of Corti (BDNF (Pax2) -KO) versus the auditory cortex and hippocampus (BDNF (TrkC) -KO). We demonstrate that BDNF (Pax2) -KO but not BDNF (TrkC) -KO mice exhibit reduced sound-evoked suprathreshold ABR waves at the level of the auditory nerve (wave I) and inferior colliculus (IC) (wave IV), indicating that BDNF in lower brain regions but not in the auditory cortex improves sound sensitivity during hearing onset. Extracellular recording of IC neurons of BDNF (Pax2) mutant mice revealed that the reduced sensitivity of auditory fibers in these mice went hand in hand with elevated thresholds, reduced dynamic range, prolonged latency, and increased inhibitory strength in IC neurons. Reduced parvalbumin-positive contacts were found in the ascending auditory circuit, including the auditory cortex and hippocampus of BDNF (Pax2) -KO, but not of BDNF (TrkC) -KO mice. Also, BDNF (Pax2) -WT but not BDNF (Pax2) -KO mice did lose basal inhibitory strength in IC neurons after acoustic trauma. These findings suggest that BDNF in the lower parts of the auditory system drives auditory fidelity along the entire ascending pathway up to the cortex by increasing inhibitory strength in behaviorally relevant frequency regions. Fidelity and inhibitory strength can be lost following auditory nerve injury leading to diminished sensory outcome and increased central noise.
authors.affiliation: Department of Auditory Neuroscience, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Vídeňská 1083, 142 20, Prague, Czech Republic.
authors.forename: Tetyana
authors.initials: T
authors.lastname: Chumak
authors.affiliation: Department of Otolaryngology, Hearing Research Centre Tübingen, Molecular Physiology of Hearing, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Rüttiger
authors.affiliation: Department of Otolaryngology, Hearing Research Centre Tübingen, Molecular Physiology of Hearing, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany.
authors.forename: Sze Chim
authors.initials: SC
authors.lastname: Lee
authors.affiliation: Department of Otolaryngology, Hearing Research Centre Tübingen, Molecular Physiology of Hearing, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany.
authors.forename: Dario
authors.initials: D
authors.lastname: Campanelli
authors.affiliation: Department of Otolaryngology, Hearing Research Centre Tübingen, Molecular Physiology of Hearing, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany.|Department of Clinical Neurobiology, University Hospital and DKFZ Heidelberg, In Neuenheimer Feld 280, 69120, Heidelberg, Germany.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Zuccotti
authors.affiliation: Department of Otolaryngology, Hearing Research Centre Tübingen, Molecular Physiology of Hearing, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany.
authors.forename: Wibke
authors.initials: W
authors.lastname: Singer
authors.affiliation: Department of Auditory Neuroscience, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Vídeňská 1083, 142 20, Prague, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Popelář
authors.affiliation: Instituto de Biologíay Genética Molecular, Universidad de Valladolid y Consejo Superior de Investigaciones Científicas, E-47003, Valladolid, Spain.
authors.forename: Katja
authors.initials: K
authors.lastname: Gutsche
authors.affiliation: Department of Otolaryngology, Hearing Research Centre Tübingen, Molecular Physiology of Hearing, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany.
authors.forename: Hyun-Soon
authors.initials: HS
authors.lastname: Geisler
authors.affiliation: Department of Otolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, Comprehensive Hearing Center, University of Würzburg, Josef-Schneider-Straße 11, 97080, Würzburg, Germany.
authors.forename: Sebastian Philipp
authors.initials: SP
authors.lastname: Schraven
authors.affiliation: Department of Otolaryngology, Hearing Research Centre Tübingen, Molecular Physiology of Hearing, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany.
authors.forename: Mirko
authors.initials: M
authors.lastname: Jaumann
authors.affiliation: DNA Genotek Inc., 2 Beaverbrook Road, Kanata, ON, K2K 1L1, Canada.
authors.forename: Rama
authors.initials: R
authors.lastname: Panford-Walsh
authors.affiliation: Centre for Integrative Neuroscience, University of Tübingen, Otfried-Müller-Straße 25, 72076, Tübingen, Germany.
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.affiliation: Instituto de Biologíay Genética Molecular, Universidad de Valladolid y Consejo Superior de Investigaciones Científicas, E-47003, Valladolid, Spain.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schimmang
authors.affiliation: Department of Otolaryngology, Hearing Research Centre Tübingen, Molecular Physiology of Hearing, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Zimmermann
authors.affiliation: Department of Auditory Neuroscience, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Vídeňská 1083, 142 20, Prague, Czech Republic.
authors.forename: Josef
authors.initials: J
authors.lastname: Syka
authors.affiliation: Department of Otolaryngology, Hearing Research Centre Tübingen, Molecular Physiology of Hearing, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany. marlies.knipper@uni-tuebingen.de.
authors.forename: Marlies
authors.initials: M
authors.lastname: Knipper
mesh_terms: D000818:Animals; D001303:Auditory Cortex / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D001309:Auditory Threshold; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003051:Cochlea / Q000378:metabolism; D016057:Evoked Potentials, Auditory, Brain Stem; D017353:Gene Deletion; D006309:Hearing; D007245:Inferior Colliculi / Q000473:pathology / Q000503:physiopathology; D019426:Integrases / Q000378:metabolism; D018345:Mice, Knockout; D009622:Noise; D011401:Promoter Regions, Genetic / Q000235:genetics; D020812:Receptor, trkC / Q000378:metabolism; D012307:Risk Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020812:Receptor, trkC; C045073:Cre recombinase; D019426:Integrases
keywords: BDNF; Central hyperactivity; High-spontaneous rate, low-threshold fibers; Homeostatic plasticity; Inferior colliculus; Sound detection threshold