Adult Cochlear Nucleus Research Articles

Effect of cochlear nerve electrocautery on the adult cochlear nucleus.

Electrocauterization and subsequent transection of the cochlear nerve induce greater injury to the cochlear nucleus than sharp transection alone. Some studies show that neurofibromatosis Type 2 (NF2) patients fit with auditory brainstem implants (ABIs) fail to achieve speech perception abilities similar to ABI recipients without NF2. Reasons for these differences remain speculative. One hypothesis posits poorer performance to surgically induced trauma to the cochlear nucleus from electrocautery. Sustained electrosurgical depolarization of the cochlear nerve may cause excitotoxic-induced postsynaptic nuclear injury. Equally plausible is that cautery in the vicinity of the cochlear nucleus induces necrosis. The cochlear nerve was transected in anesthetized adult gerbils sharply with or without bipolar electrocautery at varying intensities. Gerbils were perfused at 1, 3, 5, and 7 days postoperatively; their brainstem and cochleas were embedded in paraffin and sectioned at 10 μm. Alternate sections were stained with flourescent markers for neuronal injury or Nissl substance. In additional experiments, anterograde tracers were applied directly to a sectioned eighth nerve to verify that fluorescent-labeled profiles seen were terminating auditory nerve fibers. Cochlear nerve injury was observed from 72 hours postoperatively and was identical across cases regardless of surgical technique. Postsynaptic cochlear nucleus injury was not seen after distal transection of the nerve. By contrast, proximal transection was associated with trauma to the cochlear nucleus. Distal application of bipolar electrocautery seems safe for the cochlear nucleus. Application near the root entry zone must be used cautiously because this may compromise nuclear viability needed to support ABI stimulation.

Dynamic changes of the neurogenic potential in the rat cochlear nucleus during post-natal development

Neuronal stem cells have been described in the post-natal cochlear nucleus recently. The aim of the study was to analyse the neurogenic potential in the cochlear nucleus from the early post-natal days until adulthood. Cochlear nuclei from Sprague-Dawley rats from post-natal day P3 up to P40 were examined. Neurosphere assays showed persistent neurosphere formation from the early post-natal days until adulthood. The numbers of generated neurospheres were fewer in older ages. Neurospheres were smaller, but displayed the same pattern of neuronal stem cell markers. The markers GFAP, MBP and ß-III Tubulin showed differentiation of dissociated cells from the neurospheres in all cells of the neuronal lineage. BrdU incorporation could be detected, in an age-dependent decrease, in whole-mount experiments of the cochlear nucleus on all examined days. BrdU co-labelled with Atoh1 and ß-III Tubulin. In addition, gene expression and cellular distribution studies of the neuronal stem cell markers displayed an age-dependent reduction in both quantity and numbers. The presented results display a possible neurogenic potential until adulthood in the cochlear nucleus by in vitro and in vivo experiments. The fact that this potential is highest at a critical period of development reveals possible functional importance for the development of the cochlear nucleus and the auditory function. The persistent neurogenic potential displayed until adulthood could be a neurogenic niche in the adult cochlear nucleus, which might be used for potential therapeutic strategies.

Increased BrdU incorporation reflecting DNA repair, neuronal de-differentiation or possible neurogenesis in the adult cochlear nucleus following bilateral cochlear lesions in the rat

Neurogenesis is known to occur in response to injury in the brain, for example, as a result of neurodegenerative diseases. However, there have been few investigations into how the brain responds to damage to peripheral sensory nerves, in other areas such as the brainstem. Here, we report that bilateral surgical lesions of the cochlea result in increased incorporation of the DNA replication marker, bromodeoxyuridine (BrdU), in cells of the brainstem cochlear nucleus (CN) of the adult rat, suggesting either cell proliferation or DNA repair. Some of the BrdU-labelled cells colabelled for the mature neuron marker, NeuN and the GABAergic enzyme GAD-65, suggesting the possibility that neurogenesis might have occurred and resulted in the generation of new neurons with a GABAergic phenotype. However, some of the mature neurons also re-expressed immature neuronal intermediate filament and microtuble-associated proteins, without apoptotic neuronal death, which suggests that the colabelling of BrdU with NeuN and GAD-65 may not be a true reflection of neurogenesis, but injury-stimulated neuronal dedifferentiation. These results suggest the possibility that DNA repair, neuronal de-differentiation or possible neurogenesis occurs in the cochlear nucleus, in response to damage to the peripheral auditory system.

Recognition and Localization of Speech by Adult Cochlear Implant Recipients Wearing a Digital Hearing Aid in the Nonimplanted Ear (Bimodal Hearing)

The use of bilateral amplification is now common clinical practice for hearing aid users but not for cochlear implant recipients. In the past, most cochlear implant recipients were implanted in one ear and wore only a monaural cochlear implant processor. There has been recent interest in benefits arising from bilateral stimulation that may be present for cochlear implant recipients. One option for bilateral stimulation is the use of a cochlear implant in one ear and a hearing aid in the opposite nonimplanted ear (bimodal hearing). This study evaluated the effect of wearing a cochlear implant in one ear and a digital hearing aid in the opposite ear on speech recognition and localization. A repeated-measures correlational study was completed. Nineteen adult Cochlear Nucleus 24 implant recipients participated in the study. The participants were fit with a Widex Senso Vita 38 hearing aid to achieve maximum audibility and comfort within their dynamic range. Soundfield thresholds, loudness growth, speech recognition, localization, and subjective questionnaires were obtained six-eight weeks after the hearing aid fitting. Testing was completed in three conditions: hearing aid only, cochlear implant only, and cochlear implant and hearing aid (bimodal). All tests were repeated four weeks after the first test session. Repeated-measures analysis of variance was used to analyze the data. Significant effects were further examined using pairwise comparison of means or in the case of continuous moderators, regression analyses. The speech-recognition and localization tasks were unique, in that a speech stimulus presented from a variety of roaming azimuths (140 degree loudspeaker array) was used. Performance in the bimodal condition was significantly better for speech recognition and localization compared to the cochlear implant-only and hearing aid-only conditions. Performance was also different between these conditions when the location (i.e., side of the loudspeaker array that presented the word) was analyzed. In the bimodal condition, the speech-recognition and localization tasks were equal regardless of which side of the loudspeaker array presented the word, while performance was significantly poorer for the monaural conditions (hearing aid only and cochlear implant only) when the words were presented on the side with no stimulation. Binaural loudness summation of 1-3 dB was seen in soundfield thresholds and loudness growth in the bimodal condition. Measures of the audibility of sound with the hearing aid, including unaided thresholds, soundfield thresholds, and the Speech Intelligibility Index, were significant moderators of speech recognition and localization. Based on the questionnaire responses, participants showed a strong preference for bimodal stimulation. These findings suggest that a well-fit digital hearing aid worn in conjunction with a cochlear implant is beneficial to speech recognition and localization. The dynamic test procedures used in this study illustrate the importance of bilateral hearing for locating, identifying, and switching attention between multiple speakers. It is recommended that unilateral cochlear implant recipients, with measurable unaided hearing thresholds, be fit with a hearing aid.

Selective vulnerability of adult cochlear nucleus neurons to de-afferentation by mechanical compression

It is well established that the cochlear nucleus (CN) of developing species is susceptible to loss of synaptic connections from the auditory periphery. Less information is known about how de-afferentation affects the adult auditory system. We investigated the effects of de-afferentation to the adult CN by mechanical compression. This experimental model is quantifiable and highly reproducible. Five weeks after mechanical compression to the axons of the auditory neurons, the total number of neurons in the CN was evaluated using un-biased stereological methods. A region-specific degeneration of neurons in the dorsal cochlear nucleus (DCN) and posteroventral cochlear nucleus (PVCN) by 50% was found. Degeneration of neurons in the anteroventral cochlear nucleus (AVCN) was not found. An imbalance between excitatory and inhibitory synaptic transmission after de-afferentation may have played a crucial role in the development of neuronal cell demise in the CN. The occurrence of a region-specific loss of adult CN neurons illustrates the importance of evaluating all regions of the CN to investigate the effects of de-afferentation. Thus, this experimental model may be promising to obtain not only the basic knowledge on auditory nerve/CN degeneration but also the information relevant to the application of cochlear or auditory brainstem implants.

Specific plasticity responses to unilaterally decreased or increased hearing intensity in the adult cochlear nucleus and beyond

Variations of sensory activation in strength and pattern are known to affect structure and function of the mammalian brain. Whereas such malleability is readily granted to forebrain structures at early developmental stages, acceptance of experience-dependent structural plasticity has been slow for the adult brainstem. Over the past years we have identified consequences of cochlear ablation, noise trauma, or electrical intracochlear stimulation on neurons and circuitry of the auditory brainstem of the adult rat. We found that loss of sensory activation as well as a substitution for it entail specific molecular, ultrastructural, and morphological changes to central auditory neurons. Here, we make a first attempt to compare these different patterns of central remodeling. We tentatively suggest that after hearing loss or intracochlear stimulation responses of the central neural network in the adult brainstem suit the concept of functional adaptation.

Localization of neurotrophin-3-like immunoreactivity in the rat cochlear nucleus.

Immunohistochemistry as well as immunohistofluorescence were used to investigate the distribution of the neurotrophin-3 (NT3) in the adult rat cochlear nucleus. We found a widespread distribution of NT3 immunolabeled neurons throughout the three divisions of this nucleus. NT3-like immunoreactivity was clearly population-specific, with some cell groups heavily (various small neurons and granule cells) or moderately (large neurons of the ventral cochlear nucleus) stained, while others remained negative (a major fraction of medium and large neurons of the dorsal cochlear nucleus). Double-labeling experiments were performed using antibody against the glial fibrillary acid protein, a classic marker for mature astrocytes. This colocalization study revealed that NT3 immunoreactivity was also present in a subpopulation of astrocytes, particularly in the glia limitans and their projections. Numerous small cells also colocalized NT3 together with the glial marker in the granule cell domain and in the molecular cell layer of the dorsal cochlear nucleus. These results suggest that NT3 may exist in widespread populations of adult cochlear nucleus neurons as well as in glial cells. This abundant distribution of NT3-like immunoreactivity implies that this neurotrophin may have an important role in the continued maintenance of mature cochlear nucleus and makes it an attractive candidate for playing a role in regulation or stabilization of neuronal circuits in this nucleus.

Neurotrophin receptor immunostaining in the rat ventral cochlear nucleus

By virtue of its known segregated distribution of cell types, their known neurotransmitters and neurophysiologic properties, the cochlear nucleus is an excellent model and provides the opportunity to study the relation between neurotrophins and their receptors along with the functional properties of the adult cochlear nucleus. To investigate the potential role of neurotrophins in the mature cochlear nucleus, we determined the expression of the three major neurotrophin tyrosine kinase receptors (Trk) in the adult rat ventral cochlear nucleus, as revealed by antibodies against the full-Trk proteins. A qualitative and a cartographic analysis showed a widespread distribution of the three Trk receptors throughout the nucleus. Immunostaining was mainly restricted to neurons as shown by the lack of double immunostaining with specific markers for glial cells. However, we observed variability in immunostaining for given receptors. Three classes of cells were distinguished by their specificity for Trk receptors. The first one was a cell population that stained for TrkA or TrkB. This population characterizes the majority of small and small round neurons and fusiform cells. The second group consists of TrkC-immunolabeled cells and comprises the majority of spherical, globular, granule and small multipolar cells. The third group consists of cells that seem to be immunopositive for all three Trk receptors. This group includes in part multipolar, giant and octopus cells. A possible correlation between Trk expression and cell functional properties is suggested: TrkA- and TrkB-immunoreactive cells could include inhibitory neurons while cells stained for TrkC could include excitatory neurons. The abundant and widespread neuronal distribution of signal-transducing forms of TrkA, TrkB and TrkC predicts that their cognate ligands may exert significant effects on a large proportion of neurons within the mature ventral cochlear nucleus.

Morphology of the cochlear nucleus in CBA/J mice with chronic, severe sensorineural cochlear pathology induced during adulthood

The effects of chronic cochlear impairment on morphological features of the adult cochlear nucleus (CN) were assessed in CBA/J mice in which severe sensorineural damage had been induced by exposure to intense noise. Sections from various CN subdivisions, stained for Nissl substance and fibers, were quantitatively evaluated in four groups of noise-exposed mice that differed with regard to the age at noise exposure (2, 6, or 11 months), age at the time the CN was evaluated (6, 11, or 24 months), and the duration (chronicity) of sensorineural impairment (4, 5, 13, or 18 months). Like-aged, non-exposed CBA mice were used as controls, so the effects of peripheral damage and aging could be compared. Cochlear damage produced significant changes in CN subdivisions thought to receive the heaviest input from cochlear afferents (anteroventral CN, octopus cell area, dorsal CN layer III). These changes included a reduction of neuropil volume, reductions in neuron size, and increases in neuronal packing density that were complementary to reduced volume in these subdivisions. Effects on neuron number were minimal in all subdivisions. Central changes in noise-exposed mice were absent or diminished in DCN layers I and II, which receive relatively less input from primary fibers. The age at onset and chronicity of damage had little to do with the severity of central effects of cochlear damage. The effects of cochlear damage were not additive with age-related changes seen in the old controls.