Department of Auditory Neuroscience
Department of Auditory Neuroscience
Head: Rostislav Tureček, PhD.
Morphological and functional characteristics of nerve cells in individual auditory nuclei under normal and pathological conditions are studied in the Department. Electrophysiological and histological data are correlated with changes in the animal behavior evaluated with behavioral tests. Audiological tests and MR imaging are used to characterize age-related changes in hearing in humans.
Jiří Popelář, PhD.
Phone: +420 241 062 689
Assoc. Prof. Zbyněk Bureš, PhD.
Michaela Králíková, PhD.
Jiří Popelář, PhD.
Natalia Rybalko, PhD.
Daniel Šuta, PhD.
prof. Josef Syka, MD, DSc.
Rostislav Tureček, Ph.D.
Jana Svobodová Burianová, PhD.
Jiří Lindovský, PhD.
Oliver Profant, MD, PhD.
Milan Jilek, MSc.
Aneta Brunová, MSc.
Bohdana Hrušková, MSc.
Diana Kuchárová, MD.
Ondřej Novák, MSc.
Kateryna Pysaněnko, MSc.
Veronika Svobodová, MD.
Ondřej Zelenka, MD
Important results in 2015
1. Age-related changes in hearing
Based on the MRI recordings from auditory cortex, it seems that peripheral as well as central components of presbycusis appear to influence each other only to a limited degree. The greater extent of cortical activation in elderly subjects in comparison with young subjects, with an asymmetry towards the right side, may serve as a compensatory mechanism for the impaired processing of auditory information appearing as a consequence of ageing.
MR Unit, Department of Diagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Prague
Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles University in Prague, University Hospital Motol, Prague
Averaged cortical activity evoked by acoustic stimulation examined by fMRI in all 3 groups. YC – young controls, MP – mild presbycusis, EP – expressed presbycusis. Red colour – stimulation with pink noise centered at 350 Hz and 700 Hz; blue colour – stimulation with pink noise centered at 1.5 kHz, 3 kHz and 8 kHz. The arrowheads accentuate an increase in the right AC activation in both elderly groups.
Profant O., Tintěra J., Balogová Z., Ibrahim I., Jilek M., Syka J. (2015) Functional changes in the human auditory cortex in ageing. PLoS One. 2015 Mar 3;10(3):e0116692.
2. Deterioration of the Medial Olivocochlear Efferent System Accelerates Age-Related Hearing Loss in Pax2-Isl1 Transgenic Mice
Overexpression of transcription factor ISLET1 under the Pax2 promoter in mice manifested in hyperactivity, circling behavior, and early onset of progressive age-related hearing loss. Early age related reduction of otoacoustic emissions (DPOAEs) was found to be conditioned by deterioration of cochlear efferent terminals. Our data provide the first evidence that the alternation of MOC efferent system accelerates the age-related functional decline of hearing without the loss of OHCs.
Gabriela Pavlínková Ph.D., Laboratory of Molecular Pathogenetics, Institute of Biotechnology CAS, Prague
Prof. Bernd Fritzsch, Department of Biology, University of Iowa, Iowa City, IA, USA
Altered efferent innervations. Despite visible similarities, the quantitative analysis shows a decrease in the volume of MOC terminals of OHCs (A, C, arrows; quantified in M) and efferent vesiculated fibers in the region of Deiters’ cells (B, D, arrows; quantified in N) in young Tg+/− mice (I, M) than in WT animals (G, M). The progressive loss of efferent fibers is visible in older Tg+/− (J) compared toWT (H). In both WT and Tg+/− groups, efferent endings are missing if the OHC is lost (G, I; stars). Side view (E, F, K, L) represents the maximum projection of a focal series through the thickness of one OHC, arrows here and in B, D, H, J point out ChAT positive particles in the region of Deiters’ cells. MOC medial olivocochlear eferent system, IHC inner hair cells, OHC outer hair cells, DC Deiters’ cells, ChAT cholin acetyltransferaza.
Chumak T., Bohuslavova R., Macova I., Dodd N., Buckiova D., Fritzsch B., Syka J., Pavlinkova G. (2015) Deterioration of the Medial Olivocochlear Efferent System Accelerates Age-Related Hearing Loss in Pax2-Isl1 Transgenic Mice. Mol Neurobiol, [Epub ahead of print] DOI 10.1007/s12035-015-9215-1
GABAB receptors are the G-protein coupled receptors for the main inhibitory neurotransmitter in the brain, γ-aminobutyric acid (GABA). GABAB receptors regulate the excitability of most neurons in the central nervous system by modulating the activity of enzymes and ion channels. GABAB receptors associate with homo-oligomers of auxiliary KCTD 8, 12, 12b and 16 subunits that differentially regulate the receptor response by directly binding to the G-protein. We have shown distinct regulatory effects on G-protein signaling exerted by KCTD12 and 16 and provided evidence that GABAB/KCTD16 complexes regulate the kinetics of late inhibitory postsynaptic currents in hippocampal neurons. In summary, our data demonstrate that simultaneous assembly of distinct KCTDs at the receptor increases the molecular complexity of native GABAB receptors.
Prof. Bernhard Bettler, Department of Biomedicine, Institute of Physiology, Pharmazentrum, University of Basel, Basel, Switzerland
A, GABAB receptor subunit compositions in neurons. The principal subunits of GABAB receptors - GABAB1 (black) and GABAB2 (white) - have the prototypical seven transmembrane domains of G protein-coupled receptors. GABAB2 associates with auxiliary KCTD12 (red) or 16 (blue) subunits. B, Altered GABAB receptor responses in neurons with deleted KCTD proteins. Representative traces of GABAB agonist baclofen-evoked K+ currents recorded from cultured hippocampal neurons of WT (black), KCTD16 (red) or KCTD12 (blue) knockout mice. Deletion of KCTD12 reduces desensitization of the responses while deletion of KCTD16 leads to slightly elevated desensitization due to higher occupancy of the receptor by KCTD12. C, Superimposed traces show K+ currents evoked by 1 s-long application of baclofen to cultured hippocampal neurons isolated from WT, KCTD12 KO or KCTD16 KO mice. Bar graph summarizes the time constants obtained from a fit of the deactivation decay to a single exponential function. Note that the decay time course of the currents was significantly reduced in KCTD16 KO and unchanged in KCTD12 KO neurons, compared to WT. D, Examples of inhibitory postsynaptic currents (IPSCs) recorded from CA1 hippocampal neurons of WT or KCTD16 KO mice. Note faster decay kinetics of the currents obtained from KCTD16 KO neurons. Bar graph summarizes the time constants obtained from a fit of the deactivation decay of IPSCs to a single exponential function.
Raveh A, Turecek R and Bettler B (2015) Mechanisms of Fast Desensitization of GABAB Receptor-Gated Currents. Adv. Pharmacol. 73C:145-165.
Important results in 2014
1. Age-related changes in hearing
Hearing thresholds were examined using pure-tone audiometry over the extended frequency range 0.125–16 kHz in a large sample of men and women aged 16–70 years The results could be used to normalize hearing thresholds when comparing participants differing in age and to prepare an international standard. Magnetic resonance morphometry was used to study the state of the central auditory system in a group of elderly subjects with different degree of presbycusis. The results demonstrate significant atrophy in the auditory cortex of elderly subjects.
The MR Unit, Department of Diagnostic and Interventional Radiology of the Institute for Clinical and Experimental Medicine (IKEM), Prague
Department of Otorhinolaryngology and Head and Neck Surgery, 1st Medical Faculty of Charles University, University Hospital Motol, Prague
Audiograms. Average pure-tone audiograms in men (top) and women (bottom) grouped by their age in decades (the parameter is age group in years). The extended high-frequency range is zoomed for clarity.
Jílek M, Šuta D, Syka J, (2014): Reference hearing thresholds in an extended frequency range as a function of age and their mathematical approximation. J Acoust Soc Am. 136(4):1821–1830. IF 1.555
Profant O, Škoch A, Balogová Z, Tintěra J, Hlinka J, Syka J, (2014): Diffusion tensor imaging and MR morphometry of the central auditory pathway and auditory cortex in aging. Neuroscience 260: 87–97. IF 3.327
2. Acoustical enrichment during early postnatal development in rats improves response properties of hearing function
The study explores the effects of an acoustically enriched environment applied during the critical period of development on the responsiveness of auditory neurons in rats resulting in lower excitatory thresholds at neuronal characteristic frequency, an increased frequency selectivity, larger response magnitudes, steeper rate-intensity functions and an increased spontaneous activity. Acoustically enriched environment may permanently affect signal processing in the subcortical auditory nuclei.
Department of Electrical Engineering and Computer Science, College of Polytechnics, Jihlava
Neuronal excitatory thresholds and tuning bandwidth. Top – scatter diagrams showing the dependence of the excitatory threshold on the characteristic frequency (CF) of the neurons in the control and enriched groups of rats along with fifth-order polynomial regression curves. Bottom – scatter diagrams showing the dependence of the Q30 parameter on the CF of the neurons in the control and enriched groups of rats along with fifth-order polynomial regression curves.
Bureš Z., Bartošová J., Lindovský J., Chumak T., Popelář J., Syka J. (2014) Acoustical enrichment during early postnatal development changes response properties of inferior colliculus neurons in rats. Eur. J. Neurosci 2014, Vol. 40, pp. 3674–3683. IF 3.669
3. Molecular mechanism of GABAB receptor desensitization
We studied mechanisms of KCTD12-induced desensitization of GABAB receptor activated K+ currents. We show that the desensitization results from a dual interaction of KCTD12 with the G protein: constitutive binding stabilizes the heterotrimeric G protein at the receptor, whereas dynamic binding to the receptor-activated Gbg subunits induces desensitization by uncoupling Gbg from the effector K+ channel. Our results show that GABAB receptors are endowed with fast and reversible desensitization by harnessing KCTD12 that intercepts Gbg signaling.
Molecular mechanism of KCTD12-induced desensitization of GABAB responses.
A, Scheme illustrates the patch-clamp recording of membrane currents mediated by G-protein activated inwardly rectifying K+ channels (GIRK) from CHO cells. B, Representative traces of K+ currents activated by GABAB agonist baclofen in CHO cells expressing GABAB receptors and GIRK channels either with or without (w/o) KCTD12. KCTD12 induces pronounced and rapid desensitization of the K+ currents. C, Scheme illustrating a mechanism for fast desensitization of GABAB-activated GIRK currents. Resting (left), active (middle), and desensitized (right) states of the current response are shown. KCTD12 constitutively assembles with GABAB receptors and the G-protein into a signaling complex (inactive state). Constitutive binding of KCTD12 to activated Gβγ allows for a transient activation of GIRK channels (active state). An activity-dependent rearrangement of KCTD12 at Gβγ leads to a shielding of the GIRK-binding site on Gβγ by KCTD12 and induces current desensitization (desensitized state).
Tureček R, Schwenk J, Fritzius T, Ivánková K, Zolles G, Adelfinger L, Jacquier V, Besseyrias V, Gassmann M, Schulte U, Fakler B, Bettler B, (2014): Auxiliary GABAB Receptor Subunits Uncouple G Protein βγ Subunits from Effector Channels to Induce Desensitization. Neuron 82(5): 1032-1044. IF 15.982
Molecular mechanism of GABA B receptor regulation by KCTD proteins.
The role of GABAB receptors in animal models of tinnitus.
Mechanisms underlying complex sound processing in the neuronal assemblies in the auditory system
Pathological changes in the central auditory system accompanying aging
Molecular mechanisms responsible for generating cellular diversity in the inner ear
Project of excellence in the field of neuroscience
Processing of complex sounds in the central auditory system under normal and pathological conditions
Inernational project of GAČR 2016-2018
Cortical changes associated with presbycusis and tinnitus – MRI study.
Transcriptional regulation in neurosensory development and function in the inner ear
Targeting challenges of active ageing: innovative integrated strategies for the healing of age-related hearing loss. EU projekt FP7-PEOPLE-2013-IAPP TARGEAR, 2014-2017
Komplexní metoda vyšetřování sluchové funkce. TAČR, 2015-2016
Intergovaná měřicí platforma pro komplexní vyšetření sluchu. TAČR, 2016-2017
Bohuslavová, R., Dodd, N., Macová, I., Chumak, T., Horák, M., Syka, J., Fritzsch, B., Pavlínková, G.: (2016) Pax2-Islet1 Transgenic Mice Are Hyperactive and Have Altered Cerebellar Foliation. Mol. Neurobiol., IN PRESS
Bureš, Z., Popelář, J., Syka, J.: (2016) The effect of noise exposure during the developmental period on the function of the auditory system. Hear. Res., IN PRESS
Chumak, T., Bohuslavová, R., Macová, I., Dodd, N., Buckiová, D., Fritzsch, B., Syka, J., Pavlinková, G.: (2016) Deterioration of the Medial Olivocochlear Efferent System Accelerates Age-Related Hearing Loss in Pax2-Isl1 Transgenic Mice. Mol. Neurobiol., 53(4): 2368-2383.
Chumak, T., Rüttiger ,L., Lee, S.C., Campanelli, D., Zuccotti, A., Singer, W., Popelář, J., Gutsche, K., Geisler, H.S., Schraven, S.P., Jaumann, M., Panford-Walsh, R., Hu, J., Schimmang, T., Zimmermann, U., Syka, J., Knipper, M. (2015) BDNF in Lower Brain Parts Modifies Auditory Fiber Activity to Gain Fidelity but Increases the Risk for Generation of Central Noise After Injury. Mol. Neurobiol., IN PRESS
Jírů, F., Skoch, A., Wagnerová, D., Dezortová, M., Visková, J., Profant, O., Syka, J., Hájek, M.: (2016) The age dependence of T2 relaxation times of N-acetyl aspartate, creatine and choline in the human brain at 3 and 4T. NMR Biomed., 29(3): 284-92.
Novák, O., Zelenka, O., Hromádka, T., Syka, J.: (2016) Immediate manifestation of acoustic trauma in the auditory cortex is layer specific and cell type dependent. J. Neurophysiol, 115(4): 1860-74.
Ouda L., Burianová J. , Balogová Z., Lu H. P., Syka J.: (2016) Structural changes in the adult rat auditory system induced by brief postnatal noise exposure. Brain Struct. Funct., 221(1): 617-629.
Ouda, L., Jilek, M., Syka, J.: (2016) Expression of c-Fos in rat auditory and limbic systems following 22-kHz calls. Behav. Brain Res., 308: 196-204.
Popelář, J., Šuta, D., Lindovský, J., Bureš, Z.4, Pysanenko, K., Chumak, T., Syka, J.: (2016) Cooling of the auditory cortex modifies neuronal activity in the inferior colliculus in rats. Hear Res., 332: 7-16.
Burianová, J., Ouda, L., Syka, J.: (2015) The influence of aging on the number of neurons and levels of non-phosporylated neurofilament proteins in the central auditory system of rats. Front Aging Neurosci. 7: 27.
Chovanec, M., Zvěřina, E., Profant, O., Balogová, Z., Kluh, J, Syka, J., Lisý, J., Merunka, I., Skřivan, J., Betka, J.: (2015) Does attempt at hearing preservation microsurgery of vestibular schwannoma affect postoperative tinnitus? Biomed Res. Int. 2015: 783169.
Chumak, T., Rüttiger ,L., Lee, S.C., Campanelli, D., Zuccotti, A., Singer, W., Popelář, J., Gutsche, K., Geisler, H.S., Schraven, S.P., Jaumann, M., Panford-Walsh, R., Hu, J., Schimmang, T., Zimmermann, U., Syka, J., Knipper, M. (2015) BDNF in Lower Brain Parts Modifies Auditory Fiber Activity to Gain Fidelity but Increases the Risk for Generation of Central Noise After Injury. Mol Neurobiol. IN PRESS
Ouda, L., Profant, O., Syka, J.: (2015) Age-related changes in the central auditory system. Cell Tissue Res. 361(1): 337-358.
Profant, O., Tintěra, J., Balogová, Z., Ibrahim, I., Jilek, M., Syka, J.: (2015) Functional changes in the human auditory cortex in ageing. PLoS One 10(3):e0116692.
Raveh, A., Tureček, R., Bettler, B.: (2015) Mechanisms of fast desensitization of GABA(B) receptor-gated currents. Adv Pharmacol. 73:145-165.
Rybalko, N., Chumak, T., Bureš, Z., Popelář, J., Šuta, D., Syka, J.: (2015) Development of the acoustic startle response in rats and its change after early acoustic trauma. Behav. Brain Res. 286: 212-221.
Šuta, D., Rybalko, N., Shen, D. W., Popelář, J., Poon, P. W., Syka J.: (2015) Frequency discrimination in rats exposed to noise as juveniles. Physiol. Behav. 144: 60-65.
Tomková, M., Tomek, J., Novák, O., Zelenka, O., Syka, J., Brom, C.: (2015) Formation and disruption of tonotopy in a large-scale model of the auditory cortex. J Comput Neurosci. 39(2):131-153.
Adelfinger, L., Tureček, R., Ivankova, K., Jensen, A. A., Moss, S. J., Gassmann, M., Bettler, B.: (2014) GABAB receptor phosphorylation regulates KCTD12-induced K+ current desensitization. Biochem. Pharmacol. 91(3): 369-379.
Betka, J., Zvěřina, E., Balogová, Z., Profant, O., Skřivan, J., Kraus, J., Lisý, J., Syka, J., Chovanec, A.: (2014) Complications of microsurgery of vestibular schwannoma. Biomed. Res. Int. 2014: 315952.
Bureš, Z., Bartošová, J., Lindovský, J., Chumak, T., Popelář, J., Syka, J.: (2014) Acoustical enrichment during early postnatal development changes response properties of inferior colliculus neurons in rats. Eur. J. Neurosci. 40(11): 3674-3683.
Jilek, M., Šuta, D., Syka, J.: (2014) Reference hearing thresholds in an extended frequency range as a function of age. J. Acoust. Soc. Am. 136(4): 1821.
Ouda L., Burianová J. , Balogová Z., Lu H. P., Syka J. (2014) Structural changes in the adult rat auditory system induced by brief postnatal noise exposure. Brain Struct. Funct. In press.
Profant, O., Škoch, A., Balogová, Z., Tintěra, J., Hlinka, J., Syka, J.: (2014) Diffusion tensor imaging and MR morphometry of the central auditory pathway and auditory cortex in aging. Neurosci. 260: 87-97.
Lu, H. P., Syka, J., Chiu, T. W., Poon, P. W.: (2014) Prolonged sound exposure has different effects on increasing neuronal size in the auditory cortex and brainstem. Hear. Res. 314: 42-50.
Trojanová, J., Kulík, A., Janacek, J., Králíková, M., Syka, J., Tureček, R.: (2014) Distribution of glycine receptors on the surface of the mature calyx of Held nerve terminal. Front. Neural Circuits. 8: 120.
Tureček, R., Schwenk, J., Fritzius, T., Ivankova, K., Zolles, G., Adelfinger, L., Jacquier, V., Besseyrias, V., Gassmann, M., Schult,e U., Fakler, B., Bettler, B.: (2014) Auxiliary GABAB Receptor Subunits Uncouple G Protein βγ Subunits from Effector Channels to Induce Desensitization. Neuron. 82(5): 1032-1044.
Bureš, Z., Maršálek, P.: (2013) On the precision of neural computation with interaural level differences in the lateral superior olive.Brain Res. 1536: 16-26.
Groh, D., Seeman, P., Jilek, M., Popelář, J., Kabelka, Z., Syka, J.: (2013) Hearing function in heterozygous carriers of a pathogenic GJB2 gene mutation. Physiol. Res. 62(3): 323-330.
Chovanec, M., Zvěřina, E., Profant, O., Skřivan, J., Cakrt, O., Lisý, J., Betka, J.: (2013) Impact of video-endoscopy on the results of retrosigmoid-transmeatal microsurgery of vestibular schwannoma: prospective study. Eur. Arch. Oto-Rhino-Laryn. 270(4): 1277-1284.
Popelář, J., Rybalko, N., Burianová, J., Schwaller, B., Syka J.: (2013) The effect of parvalbumin deficiency on the acoustic startle response and prepulse inhibition in mice. Neurosci. Lett. 533: 216-220.
Profant, O., Balogová, Z., Dezortová, M., Wagnerová, D., Hájek, M., Syka, J.: (2013) Metabolic changes in the auditory cortex in presbycusis demonstrated by MR spectroscopy. Exp. Gerontol. 48(8): 795-800.
Profant, O., Burianová, J., Syka, J.: (2013) The response properties of neurons in different fields of the auditory cortex in the rat. Hear. Res. 296: 51-59.
Šuta, D., Popelář, J., Burianová, J., Syka, J.: (2013) Cortical representation of species-specific vocalizations in Guinea pig. PLoS One 8(6): e65432.
Tomek, J., Novák, O., Syka, J.: (2013) Two-Photon Processor and SeNeCA - A freely available software package to process data from two-photon calcium imaging at speeds down to several ms per frame. J. Neurophysiol. 110(1): 243-256.
Wang, T., Rusu, S. I., Hrušková, B., Tureček, R., Borst, J. G.: (2013) Modulation of synaptic depression of the calyx of Held synapse by GABAB receptors and spontaneous activity. J. Physiol. (Lond.) 591(19): 4877-4894.
Institute for Clinical and Experimental Medicine, Prague
Institute of Biotechnology Czech Academy of Science
National Chiao Tung University, Taiwan
The Czech Institute of Informatics, Robotics and Cybernetics, Czech Technical University in Prague
Motol University Hospital, Prague
Université de Bordeaux