Institute for Biology and Molecular Genetics
Thomas Schimmang

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Neurotrophin signaling

The roles of neurotrophins and their receptors for innervation of the inner ear

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 have demonstrated 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. Our 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.

Recent publications:

  • BDNF in Lower Brain Parts Modifies Auditory Fiber Activity to Gain Fidelity but Increases the Risk for Generation of Central Noise After Injury. Chumak T, Rüttiger L, Lee SC, Campanelli D, Zuccotti A, Singer W, Popelář J, Gutsche K, Geisler HS, Schraven SP, Jaumann M, Panford-Walsh R, Hu J, Schimmang T, Zimmermann U, Syka J, Knipper M.
    Mol Neurobiol. 2016 Oct;53(8):5607-27. doi: 10.1007/s12035-015-9474-x. Epub 2015 Oct 17.

  • Is there a relationship between brain-derived neurotrophic factor for driving neuronal auditory circuits with onset of auditory function and the changes following cochlear injury or during aging? Schimmang T, Durán Alonso B, Zimmermann U, Knipper M.
    Neuroscience. 2014 Dec 26;283:26-43. doi: 10.1016/j.neuroscience.2014.07.025. Epub 2014 Jul 24. Review.

  • L-type CaV1.2 deletion in the cochlea but not in the brainstem reduces noise vulnerability: implication for CaV1.2-mediated control of cochlear BDNF expression. Zuccotti A, Lee SC, Campanelli D, Singer W, Satheesh SV, Patriarchi T, Geisler HS, Köpschall I, Rohbock K, Nothwang HG, Hu J, Hell JW, Schimmang T, Rüttiger L, Knipper M.
    Front Mol Neurosci. 2013 Aug 9;6:20. doi: 10.3389/fnmol.2013.00020. eCollection 2013.

  • Noise-induced inner hair cell ribbon loss disturbs central arc mobilization: a novel molecular paradigm for understanding tinnitus. Singer W, Zuccotti A, Jaumann M, Lee SC, Panford-Walsh R, Xiong H, Zimmermann U, Franz C, Geisler HS, Köpschall I, Rohbock K, Varakina K, Verpoorten S, Reinbothe T, Schimmang T, Rüttiger L, Knipper M.
    Mol Neurobiol. 2013 Feb;47(1):261-79. doi: 10.1007/s12035-012-8372-8. Epub 2012 Nov 16.

  • Lack of brain-derived neurotrophic factor hampers inner hair cell synapse physiology, but protects against noise-induced hearing loss. Zuccotti A, Kuhn S, Johnson SL, Franz C, Singer W, Hecker D, Geisler HS, Köpschall I, Rohbock K, Gutsche K, Dlugaiczyk J, Schick B, Marcotti W, Rüttiger L, Schimmang T, Knipper M.
    J Neurosci. 2012 Jun 20;32(25):8545-53. doi: 10.1523/JNEUROSCI.1247-12.2012.


Instituto de Biología y Genética Molecular
Universidad de Valladolid - Consejo Superior de Investigaciones CIentíficas
C/ Sanz y Forés s/n
47003 - Valladolid - SPAIN
Phone: (+34) 983-184-818 Fax: (+34) 983-184-800

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