Research paper
Consequences of unilateral hearing loss: Cortical adjustment to unilateral deprivation

https://doi.org/10.1016/j.heares.2007.12.007Get rights and content

Abstract

The effect of unilateral hearing loss on 2-deoxyglucose (2-DG) uptake in the central auditory system was studied in postnatal day 21 gerbils. Three weeks following a unilateral conductive hearing loss (CHL) or cochlear ablation (CA), animals were injected with 2-DG and exposed to an alternating auditory stimulus (1 and 2 kHz tones). Uptake of 2-DG was measured in the inferior colliculus (IC), medial geniculate (MG), and auditory cortex (fields AI and AAF) of both sides of the brain in experimental animals and in anesthesia-only sham animals (SH). Significant differences in uptake, compared to SH, were found in the IC contralateral to the manipulated ear (CHL or CA) and in AAF contralateral to the CHL ear. We hypothesize that these findings may result from loss of functional inhibition in the IC contralateral to CA, but not CHL. Altered states of inhibition at the IC may affect activity in pathways ascending to auditory cortex, and ultimately activity in auditory cortex itself. Altered levels of activity in auditory cortex may explain some auditory processing deficits experienced by individuals with CHL.

Introduction

Electrophysiological investigations of conductive hearing loss (CHL) in animals have shown that CHL changes the way sound is processed in the peripheral and central auditory system (e.g., Clopton and Silverman, 1978, Webster and Bobbin, 1986, Sumner et al., 2005, Xu and Jen, 2001, Jen and Xu, 2002, Xu et al., 2007). Centrally, unilateral CHL results in a decrease in glucose uptake as measured by the 2-deoxyglucose (2-DG) method, affecting cellular activity and metabolism in the major afferent projection from the manipulated ear (e.g., Tucci et al., 1999, Tucci et al., 2001). In these animals, unilateral CHL produced by malleus removal changes the pattern of 2-DG uptake across auditory brainstem structures in a manner similar to animals that have severe cochlear damage, i.e., damage that results in a profound hearing loss.

Using a different paradigm to produce unilateral CHL (surgical atresia), Stuermer and Scheich (2000) demonstrated enhanced 2-DG uptake in primary auditory cortex (AI) but not the anterior auditory field (AAF) contralateral to the manipulated ear. In that study, gerbils’ ears were closed from postnatal day 9 (P9) until testing and sacrifice at P27. Since the onset of hearing in gerbils is approximately P12 (Finck et al., 1972, Woolf and Ryan, 1984, Ryan and Woolf, 1993), the manipulated ear never received normal stimulation after hearing onset. Pienkowski and Harrison (2005) demonstrated that in chinchilla, a precocious species with onset of hearing in utero, many basic features of auditory cortex are functional at P3 (e.g., sensitivity, firing rates, tonotopic map), yet the spectral–temporal response properties of cortical neurons continue to develop beyond P30 and into adulthood. These authors suggest that it is the postnatal acoustic environment, with its more complex sound content, that is ultimately responsible for proper cortical development.

Enhanced cortical activity has also been show to occur, at least transiently, in adult animals subsequent to chemical ablations of the cochlea (e.g., Popelar et al., 1994, Qiu et al., 2000), and partial mechanical destruction of the cochlea induces re-organization of frequency representations in the contralateral auditory cortex of adult animals (e.g., Robertson and Irvine, 1989, Rajan et al., 1993). Furthermore, neurons in auditory cortex alter their response properties subsequent to changes in stimulus pairings involved in learning and attention paradigms (e.g., Recanzone et al., 1993, Kilgard et al., 2007, Weinberger, 2007, Zatorre, 2007).

Until recently, AI and AAF were considered to be, in essence, mirror images of one another, each possessing a strict and orderly tonotopic map (e.g., Merzenich et al., 1975, Knight, 1977, Reale and Imig, 1980, Phillips and Irvine, 1982, Morel et al., 1993, Thomas et al., 1993, Stiebler et al., 1997, Rutkowski et al., 2003) and having similar anatomical connections (e.g., Anderson et al., 1980b, Imig and Reale, 1980, Imig and Morel, 1983), though AAF occupies a smaller area of cortex. This concept has been challenged in several species, based on anatomical, behavioral, and physiological evidence. For example, in cat, there are differences in the proportion of thalamic and cortical inputs to AI and AAF (e.g., Morel and Imig, 1987, Lee et al., 2004a, Lee et al., 2004b), deactivation of AI (but not AAF) disrupts performance on sound localization tasks (Jenkins and Merzenich, 1984, Lomber et al., 2007), and neurons of AI and AAF differ in their response to temporally modulated stimuli (amplitude or frequency modulated tones; Schreiner and Urbas, 1988, Tian and Rauschecker, 1994). Although responses to frequency-modulated tones can be used to differentiate AI from other regions of auditory cortex in gerbil, it does not serve to distinguish AI from AAF (Schulze et al., 1997). Other studies indicate that AI and AAF serve different roles in processing complex sounds (e.g., Linden et al., 2003, Imaizumi et al., 2004, Takahashi et al., 2005), suggesting that AAF may be specialized for rapid temporal processing (Linden et al., 2003). Presumably this specialization requires natural acoustic experience, and that normal development of auditory cortex is dependent upon the postnatal acoustic environment (Takahashi et al., 2006).

The studies mentioned above, and others, point to the differing nature of changes that can occur in the central auditory system though developmental versus adult forms of “plasticity” as a function of either peripheral or central processing mechanisms (see Calford, 2002, Syka, 2002, Irvine, 2007). In our previous reports we investigated the effects of unilateral hearing loss, typically induced in gerbils at P21 after the ear has gained some measure of acoustic “experience”, within nuclei of the auditory brainstem. Here we extend our studies to include the effect of CHL and cochlear ablation (CA) on the medial geniculate (MG) and auditory cortex (AI and AAF). For the present study, we measured glucose metabolism by the 2-DG method in animals 3 weeks after a unilateral CHL was produced by malleus removal, or after a unilateral CA in P21 gerbils. These results were compared to an anesthesia only sham group (SH) at P42. For comparison with our previous studies, we also measured glucose uptake by the inferior colliculus (IC), and in the medial geniculate (MG) in the same animals. Our primary goal was to address the question of how unilateral CHL effects metabolic activity in the contralateral auditory cortex of immature animals that have experienced approximately 10 days of normal binaural development.

Section snippets

Subjects

Eighteen Mongolian gerbils (Meriones unguiculatus), obtained from a commercial supplier (Charles Rivers), were used in this study. All anesthetic, operative, and postoperative procedures and care followed NIH guidelines, and were approved by the Institutional Animal Care Committee. All experimental procedures and tissue preparation was conducted at the University of Kansas Medical Center. Densitometry and tissue analysis was done at the Duke University Medical Center.

Each animal entered this

Results

We used uptake of 2-DG as a tool to measure activity within the auditory midbrain and forebrain of young gerbils 3 weeks after a unilateral hearing loss produced by middle (conductive) or inner (sensorineural) ear manipulation. We found significant left–right (ipsilateral–contralateral) differences between the IC’s subsequent to either manipulation, and the activity in contralateral IC differed significantly from SH in both conditions. No significant change in glucose uptake was observed in the

Discussion

Overall the results of this study conform to our earlier investigations, showing that unilateral CHL (and CA) significantly reduce glucose activity in the contralateral IC (e.g., Tucci et al., 1999). At the level of auditory cortex, CHL significantly reduces activity in the contralateral AAF. This suggests that conductive impairment does have a measurable effect on auditory cortex, and thus may contribute to potential cognitive dysfunctions related to processing sounds and speech. To explain

References (90)

  • P.H.-S. Jen et al.

    Monaural middle ear destruction in juvenile and adult mice: effects on responses to sound direction in the inferior colliculus ipsilateral to the intact ear

    Hear. Res.

    (2002)
  • M.P. Kilgard et al.

    Experience dependent plasticity alters cortical synchronization

    Hear. Res.

    (2007)
  • P.A. Knight

    Representation of the cochlea in the anterior auditory field (AAF) of the cat

    Brain Res.

    (1977)
  • S.G. Lomber et al.

    Functional specialization in non-primary auditory cortex of the cat: areal and laminar contributions to sound localization

    Hear. Res.

    (2007)
  • J.E. Mossop et al.

    Down-regulation of inhibition following unilateral deafening

    Hear. Res.

    (2000)
  • D.P. Phillips et al.

    Properties of single neurons in the anterior auditory field (AAF) of cat cerebral cortex

    Brain Res.

    (1982)
  • J. Popelar et al.

    Plastic changes in ipsi-contralateral differences and inferior colliculus evoked potentials after in the adult guinea pig of auditory cortex injury to one ear

    Hear. Res.

    (1994)
  • C.X. Qiu et al.

    Inner hair cell loss leads to enhanced response amplitudes in auditory cortex of unanaesthetized chinchillas: evidence for increased system gain

    Hear. Res.

    (2000)
  • R. Rutkowski et al.

    Characterization of multiple physiological fields within the anatomical core of rat auditory cortex

    Hear. Res.

    (2003)
  • C.T. Sasaki et al.

    Differential [′4C]2-deoxyglucose uptake after deafferentation of the mammalian auditory pathway – a model for examining tinnitus

    Brain Res.

    (1980)
  • H. Scheich et al.

    The cognitive auditory cortex: task-specificity of stimulus representations

    Hear. Res.

    (2007)
  • I.W. Stuermer et al.

    Early unilateral auditory deprivation increases 2-deoxyglucose uptake in contralateral auditory cortex of juvenile Mongolian gerbils

    Hear. Res.

    (2000)
  • H. Takahashi et al.

    Interfield differences in intensity and frequency representation of evoked potentials in rat auditory cortex

    Hear. Res.

    (2005)
  • D. Wilmington et al.

    Binaural processing after corrected congenital unilateral conductive hearing loss

    Hear. Res.

    (1994)
  • N.M. Weinberger

    Auditory associative memory and representational plasticity in the primary auditory cortex

    Hear. Res.

    (2007)
  • W. Wetzel et al.

    Right auditory cortex lesion in Mongolian gerbils impairs discrimination of rising and falling frequency-modulated tones

    Neurosci. Lett.

    (1998)
  • N.K. Woolf et al.

    Cochlear and middle ear effects on metabolism in the central auditory pathway during silence: a 2-deoxyglucose study

    Brain Res.

    (1983)
  • N.K. Woolf et al.

    The development of auditory function in the cochlea of the Mongolian gerbil

    Hear. Res.

    (1984)
  • N.K. Woolf et al.

    Ontogeny of neuronal discharge patterns in the ventral cochlear nucleus of the Mongolian gerbil

    Brain Res.

    (1985)
  • Z.-Y. Yu et al.

    Changes in neocortical and hippocampal GABAA receptor subunit distribution during brain maturation and aging

    Brain Res.

    (2006)
  • R.J. Zatorre

    There’s more to auditory cortex than meets the ear

    Hear. Res.

    (2007)
  • L.M. Aitkin et al.

    The interplay of excitation and inhibition in the cat medial geniculate body

    J. Neurophysiol.

    (1968)
  • L.M. Aitkin et al.

    Medial geniculate body: unit responses in awake cat

    J. Neurophysiol.

    (1974)
  • L.M. Aitkin et al.

    Medial geniculate body of the cat: organization and responses to tonal stimuli of neurons in the ventral division

    J. Neurophysiol.

    (1972)
  • R.A. Anderson et al.

    The efferent projections of the central nucleus and pericentral nucleus of the inferior colliculus in the cat

    J. Comp. Neurol.

    (1980)
  • R.A. Anderson et al.

    The thalamocortical and corticothalamic connections of AI, AII, and the anterior auditory field (AAF) in the cat: evidence for two largely segregated systems of connections

    J. Comp. Neurol.

    (1980)
  • E. Budinger et al.

    Functional organization of auditory cortex in the Mongolian gerbil (Meriones unguiculatus). III. Anatomical subdivisions and corticocortical connections

    Eur. J. Neurosci.

    (2000)
  • D. Caird et al.

    Functional organization of auditory cortical fields in the Mongolian gerbil (Meriones unguiculatus): binaural 2-deoxyglucose patterns

    J. Comp. Physiol. A

    (1991)
  • M.B. Calford

    The parcellation of the medial geniculate body of the cat defined by auditory response properties of single units

    J. Neurosci.

    (1983)
  • N.B. Cant et al.

    Organization of the inferior colliculus of the gerbil (Meriones unguiculatus): differences in distribution of projections from the cochlear nuclei and the superior olivary complex

    J. Comp. Neurol.

    (2006)
  • B.M. Clopton et al.

    Changes in latency and duration of neural responding following developmental auditory deprivations

    Exp. Brain Res.

    (1978)
  • A. Finck et al.

    Development of cochlear function in the neonate Mongolian gerbil (Meriones unguiculatus)

    J. Comp. Physiol. Psychol.

    (1972)
  • W-J. Gao et al.

    Development of inhibitory circuitry in visual and auditory cortex of postnatal ferrets: immunocytochemical localization of GABAergic neurons

    J. Comp. Neurol.

    (1999)
  • Hutson, K., Benson, C., Cant, N., 2004. Anatomical definition of auditory cortex in the gerbil. Assoc. Res....
  • K. Imaizumi et al.

    Modular functional organization of cat anterior auditory field

    J. Neurophysiol.

    (2004)
  • Cited by (27)

    • Behavioural performance and self-report measures in children with unilateral hearing loss due to congenital aural atresia

      2021, Auris Nasus Larynx
      Citation Excerpt :

      Children do not reach adult performance before adolescence [13,14], consistent with physiological evidence for the maturational processes within the auditory system [15]. Bilateral sensorineural hearing loss (SNHL) during development is associated with changes in the neural processing of sounds measured in late childhood/adolescence [16], but there is conflicting evidence about the impact of conductive UHL on auditory system development [17–19]. Children with bilateral mild hearing loss (20–40 dB HL > 2 kHz) may present with poor speech recognition in quiet/noise and localisation difficulties, and are also at risk for language development delays or/and academic difficulties [20].

    • Using acoustic reflex threshold, auditory brainstem response and loudness judgments to investigate changes in neural gain following acute unilateral deprivation in normal hearing adults

      2017, Hearing Research
      Citation Excerpt :

      In addition, these studies investigated changes in neural activity after noise trauma (Dong et al., 2010; Salvi et al., 1990). However, there are deprivation studies (involving transient conductive hearing loss) in animals that have shown effects that are consistent with the ABR findings in the present study (Hutson et al., 2008, 2009). For example, Hutson et al. (2009) reported a significant reduction in neural activity in adult gerbils (as measured by 2-deoxy-glucose uptake) 1 week after mild unilateral conductive hearing loss (removal of the malleus), in the afferent auditory pathway relative to the affected ear.

    • Neurofilament heavy chain expression and neuroplasticity in rat auditory cortex after unilateral and bilateral deafness

      2016, Hearing Research
      Citation Excerpt :

      They showed significantly decreased glucose metabolism in the cochlear nucleus, however, higher auditory pathways did not show changes during their short study period. Hutson et al. showed similar results in unilaterally deafened gerbils (Hutson et al., 2008). In this regard, a future study with a longer duration of deafness should be performed to further evaluate auditory cortical plastic changes.

    • Loudness modulation after transient and permanent hearing loss: Implications for tinnitus and hyperacusis

      2014, Neuroscience
      Citation Excerpt :

      Cortical-evoked thresholds returned to levels similar to those for controls in a subgroup of deprived animals after 3 weeks of exposure to ambient noise following the 8 months of deprivation. Studies investigating physiological modifications in monaural deprivation have found decreases in 2-deoxycglucose (2-DG) uptake in the deprived ear pathway, including the anteroventral cochlear nucleus (AVCN), IC, MG, AI, and anterior auditory field (AAF) compared to control animals, but no alteration in the medial superior olive (MSO) (Hutson et al., 2008, 2009) (see Table 3). Glucose utilization in the auditory pathway of the open ear (contralateral to the deprived ear) has shown a different pattern, with decrease in the IC, MG and AI, more utilization in the MSO, and no modification in the AVCN and AAF (see Table 3).

    • Whisker stimulation increases expression of nerve growth factor- and interleukin-1β-immunoreactivity in the rat somatosensory cortex

      2010, Brain Research
      Citation Excerpt :

      The major finding reported here is that whisker stimulation enhances the number of NGF and IL1β-IR neurons in the Sctx. However, these changes were not observed in the auditory cortex, since each side of the cortex receives sensory inputs from both ears (Hutson et al., 2008). Previously it was shown that epileptic activity increases expression of NGF (Gall and Isackson, 1989; Zafra et al., 1990; Ernfors et al., 1991) and IL1β (Eriksson et al., 2000; Ravizza et al., 2006) and whisker stimulation increases NGF mRNA levels (Schwarting et al., 1994) and the number of TNF-IR cells in the Sctx (Churchill et al., 2008).

    • Acoustic startle and prepulse inhibition in the Mongolian gerbil

      2009, Physiology and Behavior
      Citation Excerpt :

      The peripheral auditory system [25,26] and many aspects of central auditory processing [27,28] are well described. Gerbils are frequently used in developmental studies [29,30], in studies investigating hearing loss [31] and regeneration [32,33]. Gerbils have also been investigated for general aspects of domestication as two different strains are available: the domesticated strain commonly used in laboratory research, and a strain descending from wild-type gerbils captured in 1995.

    View all citing articles on Scopus
    View full text