Skip to main content

Advertisement

SpringerLink
Log in

Expression of c-fos in auditory and non-auditory brain regions of the gerbil after manipulations that induce tinnitus

  • Research Article
  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Abstract

Subjective tinnitus is a phantom sound sensation that does not result from acoustic stimulation and is audible to the affected subject only. Tinnitus-like sensations in animals can be evoked by procedures that also cause tinnitus in humans. In gerbils, we investigated brain activation after systemic application of sodium salicylate or exposure to loud noise, both known to be reliable tinnitus-inductors. Brains were screened for neurons containing the c-fos protein. After salicylate injections, auditory cortex was the only auditory area with consistently increased numbers of immunoreactive neurons compared to controls. Exposure to impulse noise led to prolonged c-fos expression in auditory cortex and dorsal cochlear nucleus. After both manipulations c-fos expression was increased in the amygdala, in thalamic midline, and intralaminar areas, in frontal cortex, as well as in hypothalamic and brainstem regions involved in behavioral and physiological defensive reactions. Activation of these non-auditory areas was attributed to acute stress, to aversive-affective components and autonomous reactions associated with the treatments and a resulting tinnitus. The present findings are in accordance with former results that provided evidence for suppressed activation in auditory midbrain but enhanced activation of the auditory cortex after injecting high doses of salicylate. In addition, our present results provide evidence that acute stress coinciding with a disruption of hearing may evoke activation of the auditory cortex. We interpret these results in favor of our model of central tinnitus generation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.

Similar content being viewed by others

References

  • Andersson G, Lyttkens L, Hirvela C, Furmark T, Tillfors M, Fredrikson M (2000) Regional cerebral blood flow during tinnitus: a PET case study with lidocaine and auditory stimulation. Acta Otolaryngol 120:967–972

    Article  CAS  PubMed  Google Scholar 

  • Arnauld E, Jeantet Y, Arsaut J, Demotes-Mainard J (1996) Involvement of the caudal striatum in auditory processing: c-fos response to cortical application of picrotoxin and to auditory stimulation. Mol Brain Res 41:27–35

    Article  CAS  PubMed  Google Scholar 

  • Arnold W, Bartenstein P, Oestreicher E, Römer W, Schwaiger M (1996) Focal metabolic activation in the predominant left auditory cortex in patients suffering from tinnitus: A PET study with [18F]deoxyglucose. ORL J Otorhinolaryngol Relat Spec 58:195–199

    CAS  PubMed  Google Scholar 

  • Bauer CA, Brozoski TJ (2001) Assessing tinnitus and prospective tinnitus therapeutics using a psychophysical animal model. J Assoc Res Otolaryngol 2:54–64

    CAS  PubMed  Google Scholar 

  • Budinger E, Heil P, Scheich H (2000) Functional organization of auditory cortex in the mongolian gerbil (Meriones unguiculatus). IV. Connections with anatomically characterized subcortical structures. Eur J Neurosci 12:2452–2474

    Article  CAS  PubMed  Google Scholar 

  • Carretta D, Hervé-Minvielle A, Bajo VM, Villa AE, Rouiller EM (1999) C-fos expression in the auditory pathways related to the significance of acoustic signals in rats performing a sensory-motor task. Brain Res 841:170–183

    Article  CAS  PubMed  Google Scholar 

  • Dayas CV, Buller KM, Day TA (1999) Neuroendocrine responses to an emotional stressor: evidence for involvement of the medial but not the central amygdala. Eur J Neurosci 11:2312–2322

    Article  CAS  PubMed  Google Scholar 

  • Friauf E (1995) C-fos immunocytochemical evidence for acoustic pathway mapping in rats. Exp Brain Res 66:217–224

    Article  CAS  Google Scholar 

  • Galeno TM, Van Hoesen HG, Brody MJ (1984) Central amygdaloid nucleus lesions attenuates exaggerated hemodynamic responses to noise stress in spontaneously hypertensive rat. Brain Res 291:249–259

    Article  CAS  PubMed  Google Scholar 

  • Goldstein LE, Rasmusson AM, Bunney BS, Roth RH (1996) Role of the amygdala in the coordination of behavioral, neuroendocrine, and prefrontal cortical monoamine responses to psychological stress in the rat. J Neurosci 16:4787–4798

    CAS  PubMed  Google Scholar 

  • Heffner HE, Harrington IA (2002) Tinnitus in hamsters following exposure to intense sound. Hear Res 170:83–95

    Article  PubMed  Google Scholar 

  • Hudson AJ (2000) Pain perception and response: central nervous system mechanisms. Can J Neurol Sci 27:2–16

    CAS  PubMed  Google Scholar 

  • Jastreboff PJ, Sasaki CT (1994) An animal model of tinnitus: a decade of development. Am J Otol 15:19–27

    CAS  PubMed  Google Scholar 

  • Joels M, de Kloet R (1992) Control of neuronal excitability by corticosteroid hormones. Trends Neurosci 15:25–30

    Article  CAS  PubMed  Google Scholar 

  • Jolkkonen E, Pitkänen A (1998) Intrinsic connections of the rat amygdaloid complex: Projections originating in the central nucleus. J Comp Neurol 395:53–72

    Article  CAS  PubMed  Google Scholar 

  • Langner G, Wallhäusser-Franke E (1999) Computer simulation of a tinnitus model based on labelling of tinnitus activity in the auditory cortex. In: Hazell J (ed) Proceedings of the Sixth International Tinnitus Seminar, The Tinnitus and Hyperacusis Centre, London 1999, pp 20–25

  • LeDoux JE (2000) Emotion circuits in the brain. Ann Rev Neurosci 23:155–184

    Google Scholar 

  • Linke R (1999a) Organization of projections to temporal cortex originating in the thalamic posterior intralaminar nucleus of the rat. Exp Brain Res 127:314–320

    Article  CAS  PubMed  Google Scholar 

  • Linke R (1999b) Differential projection patterns of superior and inferior collicular neurons onto posterior paralaminar nuclei of the thalamus surrounding the medial geniculate body in the rat. Eur J Neurosci 11:187–203

    CAS  PubMed  Google Scholar 

  • Lockwood AH, Salvi RJ, Coad ML, Towsley ML, Wack DS, Murphy BW (1998) The functional neuroanatomy of tinnitus—evidence for limbic system links and neural plasticity. Neurology 50:114–120

    CAS  PubMed  Google Scholar 

  • McGaugh JL, Cahill L, Roozendaal B (1996) Involvement of the amygdala in memory storage: Interaction with other brain systems. Proc Natl Acad Sci U S A 93:13508–13514

    CAS  PubMed  Google Scholar 

  • Müller M, Klinke R, Arnold W, Oestreicher E (2003) Auditory nerve fiber responses to salicylate revisited. Hearing Res 183:37–43

    Google Scholar 

  • Neophytu SI, Graham M, Williams J, Aspley S, Marsden CA, Beckett SR (2000) Strain differences to the effects of aversive frequency ultrasound on behaviour and brain topography of c-fos expression in the rat. Brain Res 854:158–164

    Article  PubMed  Google Scholar 

  • Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic, San Diego

  • Porro CA, Cavazzuti M, Baraldi P, Giuliani D, Panerai AE, Corazza R (2000) CNS pattern of metabolic activity during tonic pain: evidence for modulation by β-endorphin. Eur J Neurosci 11:874–888

    Article  Google Scholar 

  • Radulovic J, Kammermeier J, Spiess J (1998) Relationship between Fos production and classical fear conditioning: Effects of novelty, latent inhibition, and unconditioned stimulus preexposure. J Neurosci 18:7452–7461

    CAS  PubMed  Google Scholar 

  • Raphael RM, Nguyen TA, Yong C, Stebe K, Popel AS (2000) Salicylate interactions with lipids: The mechanism for salicylate inhibition of electromotility? Assoc Res Otolaryngol 23:5743

    Google Scholar 

  • Roozendal B, Koolhaas JM, Bohus B (1997) The role of the central amygdala in stress and adaption. Acta Physiol Scand Suppl 640:51–54

    PubMed  Google Scholar 

  • Scheich H, Heil P, Langner G (1993) Functional organization of auditory cortex in the mongolian gerbil (Meriones unguiculatus) II. Tonotopic 2-deoxyglucose. Eur J Neurosci 5:898–914

    CAS  PubMed  Google Scholar 

  • Slepecky N (1986) Overview of mechanical damage to the inner ear: noise as a tool to probe cochlear function. Hear Res 22:307–321

    Article  CAS  PubMed  Google Scholar 

  • Sukov W, Barth DS (2002) Cellular mechanisms of thalamically evoked gamma oscillations in auditory cortex. J Neurophysiol 85:1235–1245

    Google Scholar 

  • Tischmeyer W, Grimm R (1999) Activation of immediate early genes and memory formation. Cell Mol Life Sci 55:564–574

    CAS  PubMed  Google Scholar 

  • Touma JB (1992) Controversies in noise-induced hearing loss (NIHL). Ann Occup Hyg 36:199–209

    CAS  PubMed  Google Scholar 

  • Wallhäusser-Franke E (1997) Salicylate evokes c-fos expression in the brainstem, implications for tinnitus. Neuroreport 8:725–728

    CAS  PubMed  Google Scholar 

  • Wallhäusser-Franke E, Langner G (2001) Phantom sounds: mechanisms of tinnitus in the central nervous system. Neuroforum 7:21–27

    Google Scholar 

  • Wallhäusser-Franke E, Braun S, Langner G (1996) Salicylate alters 2-DG uptake in the auditory system: A model for tinnitus? Neuroreport 7:1585–1588

    PubMed  Google Scholar 

  • Zuschratter W, Gass P, Herdegen T, Scheich H (1995) Comparison of frequency-specific c-fos expression and fluoro-2-deoxyglucose uptake in auditory cortex of gerbils (Meriones unguiculatus). Eur J Neurosci 7:1614–1626

    CAS  PubMed  Google Scholar 

Download references

Acknowledgement

This study was supported by a prize of the Messer-Foundation to E. W.-F.

Author information

Authors and Affiliations

  1. Department of Neuroacoustics, Institute of Zoology, Darmstadt University of Technology, Schnittspahnstr. 3, 64287, Darmstadt, Germany

    E. Wallhäusser-Franke, C. Mahlke, R. Oliva, S. Braun, G. Wenz & G. Langner

Authors
  1. E. Wallhäusser-Franke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Mahlke
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. Oliva
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. Braun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. Wenz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G. Langner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. Wallhäusser-Franke.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wallhäusser-Franke, E., Mahlke, C., Oliva, R. et al. Expression of c-fos in auditory and non-auditory brain regions of the gerbil after manipulations that induce tinnitus. Exp Brain Res 153, 649–654 (2003). https://doi.org/10.1007/s00221-003-1614-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00221-003-1614-2

Keywords

Search

Navigation