Zhengnong Chen

Is duration tuning a transient process in the inferior colliculus of guinea pigs

Duration selectivity appears to be a fundamental neural encoding mechanism found throughout the animal kingdom. Previous studies reported that band-pass duration-tuned neurons typically show offset responses and occupy a small portion of auditory neurons in non-echolocation mammals relative to echolocation bats. Therefore, duration tuning is generally weaker in non-echolocation mammals. In the present study, duration tuning was analyzed for 207 neurons recorded in the inferior colliculus (IC) of guinea pigs. Duration tuning was found to be stronger in the onset component of the responses from sustained, on-off and pause neurons than had been reported previously, when a short analysis window was applied. The need for an appropriate time window for duration tuning analysis was also supported by the fact that the on and off responses from an on-off neuron may show different duration tuning features. Therefore, duration tuning appears to be a transient neural coding process in the IC of guinea pigs. Duration tuning for these types of neurons may have been blurred by the use of a relatively unselective, long window.

Local inhibition shapes duration tuning in the inferior colliculus of guinea pigs

Neural tuning to sound durations is a useful filter for the identification of a variety of sounds. Previous studies have shown that the interaction between excitatory and inhibitory inputs plays a role in duration selectivity in echolocating bats. However, this has not been investigated in non-echolocating mammals. In the inferior colliculus (IC) of these mammals, it is recognized that the excitatory responses to sounds are mediated through AMPA and NMDA receptors while the inhibitory input is mediated through gamma-aminobutyric acid (GABA) and glycine receptors. The present study explores the potential interplay between inhibitory and excitatory inputs and its role in the duration selectivity of IC neurons in guinea pigs. It was found that the application of bicuculline (BIC, a GABA A blocker) and/or strychnine (STRY, a glycine blocker) eliminated or reduced duration tuning in most units that were duration tuned (32 out of 39 for BIC, 50 out of 64 for STRY, respectively). The inhibitory input (either by GABA or by glycine) appeared to have a stronger regulating effect on the early excitation mediated by AMPA than on later excitation by NMDA. This is more distinguishable in neurons that show duration selectivity. In conclusion, the inhibitory effect on the early responses appears to be the main contributor for the duration selectivity of the IC in guinea pigs; potential mechanisms for this duration selectivity are also discussed.

Triple semicircular canal occlusion for the treatment of Meniere's disease

Conclusion. Triple semicircular canal occlusion (TSCO) controls vertigo, is easy to perform, and could be used as an alternative procedure for the treatment of Ménières disease in selected patients who complain mainly of intractable vertigo. Objective. To seek an effective alternative surgical procedure for treating Ménières disease in selected patients with intolerant rotational vertigo. Patients and methods. Three patients with Ménières disease who underwent unsuccessful endolymphatic sac decompression or mastoid shunt, then underwent TSCO. Vertigo control and vestibular and auditory function were measured. Results. The early vestibular symptoms caused by surgery resolved quickly and no hearing deterioration occurred after surgery. At the end of the follow-up period, based on the AAO-HNS criteria, two cases had complete control of vertigo (class A) and the other had substantial control of vertigo attacks (class B). Hearing was similar to the preoperative level at the end of the follow-up period.

The effect of noise-induced sloping high-frequency hearing loss on the gap-response in the inferior colliculus and auditory cortex of guinea pigs

Gap detection has been used as an evaluation tool for temporal processing in subjects with sensorineural hearing loss (SNHL). However, the results from other reports are varied making it difficult to clearly define the impact of SNHL on the temporal processing ability of the auditory system. Specifically, we do not know if and how a high-frequency hearing loss impacts, presumably through off-channel interaction, the temporal processing in low-frequency channels where hearing sensitivity is virtually normal. In this experiment, gap-evoked responses in a low-frequency band (0.5-8 kHz) were recorded in the inferior colliculus (IC) and auditory cortex (AC) of guinea pigs through implanted electrodes, before and after a slopping high-frequency hearing loss, which was induced by over-stimulation using a 12-kHz-tone. The results showed that the gap thresholds in the low-frequency region increased gradually and became significantly higher 8 weeks after the induced high-frequency hearing loss. In addition, the response latency was slightly increased in the IC but this was not true for the AC. These results strongly indicate that a high-frequency hearing loss exerted an off-channel impact on temporal processing in the low-frequency region of the auditory system.

Topographic and quantitative evaluation of gentamicin-induced damage to peripheral innervation of mouse cochleae

Ototoxicity induced by aminoglycoside antibiotics appears to occur both in hair cells (HCs) and the cochlear nerves that innervate them. Although HC loss can be easily quantified, neuronal lesions are difficult to quantify because two types of afferent dendrites and two types of efferent axons are tangled beneath the hair cells. In the present study, ototoxicity was induced by gentamicin in combination with the diuretic agent furosemide. Neuronal lesions were quantified in cochlear whole-mount preparations combined with microsections across the habenular perforate (HP) openings to achieve a clear picture of the topographic relationship between neuronal damage and HC loss. Multiple immunostaining methods were employed to differentiate the two types of afferent dendrites and two types of efferent axons. The results show that co-administration of gentamicin and furosemide resulted in a typical dynamic pattern of HC loss that spread from the basal turn to the outer hair cells to the apex and inner hair cells, depending on the dose and survival time after drug administration. Lesions of the innervation appeared to occur at two stages. At the early stage (2-4 days), the loss of labeling of the two types of afferent dendrites was more obvious than the loss of labeled efferent axons. At the late stage (2-4 weeks), the loss of labeled efferent axons was more rapid. In the high-dose gentamicin group, the loss of outer HCs was congruent with afferent dendrite loss at the early stage and efferent axon loss at the late stage. In the low-dose gentamicin group, the loss of labeling for cochlear innervation was more severe and widespread. Thus, we hypothesize that the gentamicin-induced damage to cochlear innervation occurs independently of hair cell loss.

Bilirubin induces auditory neuropathy in neonatal guinea pigs via auditory nerve fiber damage

Bilirubin can cause temporary or permanent sensorineural deafness in newborn babies with hyperbilirubinemia. However, the underlying targets and physiological effects of bilirubin‐induced damage in the peripheral auditory system are unclear. Using cochlear functional assays and electron microscopy imaging of the inner ear in neonatal guinea pigs, we show here that bilirubin exposure resulted in threshold elevation in both compound action potential (CAP) and auditory brainstem response (ABR), which was apparent at 1 hr and peaked 8 hr after drug administration. The threshold elevation was associated with delayed wave latencies and elongated interwave intervals in ABR and CAP. At 72 hr postinjection, these measures returned to control levels, except for the CAP amplitude. Cochlear microphonics remained unchanged during the experiment. Morphological abnormalities were consistent with the electrophysiological dysfunction, revealing fewer auditory nerve fibers (ANFs) in the basal turn, myelin sheath lesions of spiral ganglion neurons (SGNs) and ANFs, and loss of type 1 afferent endings beneath inner hair cells (IHCs) without loss of hair cells at 8 hr posttreatment. Similar to the electrophysiological findings, morphological changes were mostly reversed 10 days after treatment, except for the ANF reduction in the basal turn. These results suggest that hyperbilirubinemia in neonatal guinea pigs impaired auditory peripheral neuromechanisms that targeted mainly the IHC synapses and the myelin sheath of SGNs and their fibers. Our observations indicate a potential connection between hyperbilirubinemia and auditory neuropathy.

Comparison of Cochlear Cell Death Caused by Cisplatin, Alone and in Combination with Furosemide

Establishment of appropriate animal models is an important step in exploring the mechanisms of drug-induced ototoxicity. In the present study, using guinea pigs we compared cochlear lesions induced by cisplatin administered in two regimens: consecutive application alone and in combination with furosemide. The effects of furosemide alone were also evaluated; it was found to cause temporary hearing loss and reversible damage to the stria vascularis. Consecutive application of cisplatin alone appeared to be disadvantageous because it resulted in progressive body weight loss and higher mortality compared to the combined regimen, which used a smaller cisplatin dose. The combined regimen resulted in comparable hearing loss and hair cell loss but a markedly lower mortality. However, their coadministration failed to cause similar damage to spiral ganglion neurons (SGN), as seen in animals that received cisplatin alone. This difference suggests that the combined regimen did not mimic the damage to cochlear neuronal innervation caused by the clinical application of cisplatin. The difference also suggests that the SGN lesion is not caused by cisplatin entering the cochlea via the stria vascularis.

Categories of Auditory Performance and Speech Intelligibility Ratings of Early-Implanted Children without Speech Training

Objective To assess whether speech therapy can lead to better results for early cochlear implantation (CI) children. Patients A cohort of thirty-four congenitally profoundly deaf children who underwent CI before the age of 18 months at the Sixth Hospital affiliated with Shanghai Jiaotong University from January 2005 to July 2008 were included. Nineteen children received speech therapy in rehabilitation centers (ST), whereas the remaining fifteen cases did not (NST), but were exposed to the real world, as are normal hearing children. Methods All children were assessed before surgery and at 6, 12, and 24 months after surgery with the Categories of Auditory Performance test (CAP) and the Speech Intelligibility Rating (SIR). Each assessment was given by the same therapist who was blind to the situation of the child at each observation interval. CAP and SIR scores of the groups were compared at each time point. Results Our study showed that the auditory performance and speech intelligibility of trained children were almost the same as to those of untrained children with early implantation. The CAP and SIR scores of both groups increased with increased time of implant use during the follow-up period, and at each time point, the median scores of the two groups were about equal. Conclusions These results indicate that great communication benefits are achieved by early implantation (<18 months) without routine speech therapy. The results exemplify the importance of enhanced social environments provided by everyday life experience for human brain development and reassure parents considering cochlear implants where speech training is unavailable.

Protein kinase A and C signaling induces bilirubin potentiation of GABA/glycinergic synaptic transmission in rat ventral cochlear nucleus neurons.

Previous studies have suggested that bilirubin can potentiate GABA/glycinergic synaptic transmission in lateral superior olivary nucleus neurons, but the cellular mechanism has not been defined. The present study evaluated the possible roles of protein kinase A (PKA) and C (PKC) in bilirubin potentiation of GABA/glycinergic synaptic transmission in rat ventral cochlear nucleus (VCN) neurons. VCN neurons were acutely isolated from postnatal 10-12-day-old (P10-12) rats and were voltage-clamped in whole-cell mode. Miniature inhibitory postsynaptic currents (mIPSC) frequencies, but not amplitude, were increased by bilirubin. Forskolin (PKA activator) and H-89 (PKA inhibitor) also individually increased mIPSCs frequency, with an additional increase induced by co-incubation with bilirubin and H-89. Pretreatment with forskolin blocked bilirubin potentiation. mIPSC frequency was not altered by phorbol 12,13-diacetate (PKC activator), but mIPSC frequency was increased following co-application of bilirubin. The mIPSC frequency was increased by chelerythrine (PKC inhibitor), and then further increased after the addition of bilirubin. Neither H-89, forskolin, nor PDA, nor their co-application with bilirubin affected mIPSC amplitudes of GABA-activated (I(GABA))/glycine-activated (I(gly)) currents, suggesting a presynaptic locus of activity. Chelerythrine decreased the mIPSC amplitudes and I(GABA)/I(gly), suggesting a postsynaptic locus of activity. These data suggest that both PKA and PKC can modulate GABA and glycine release in rat VCN neurons. Bilirubin facilitates transmitter release via presynaptic PKA activation, which might provide insight into the cellular mechanism underlying bilirubin-induced hearing dysfunction.

Important factors for the hearing loss caused by the triple semicircular canal occlusion in guinea pigs.

Dynamic recording of the auditory brainstem response is helpful in verifying harmful procedure(s) to hearing during triple semicircular canal occlusion (TSCO) surgery. The damage to the membranous semicircular labyrinth is the single major contributor to hearing loss caused by TSCO. Background: Posterior semicircular canal occlusion has been recognized as an efficient method of eliminating vertigo without causing a significant hearing impairment. Recently, TSCO has also been explored for its potential to treat vertigo of various causes. In limited animal studies, varied hearing impairments have been documented after TSCO. However, the major factor(s) causing hearing loss in TSCO is/are unclear. Methods: Triple semicircular canal occlusion was performed on 36 guinea pigs in total. The cochlear function of the guinea pigs was monitored by observing the auditory brainstem response. The impact of membranous labyrinth damage on hearing was verified by a between-group comparison. Results: Hearing loss during TSCO was accumulated in every step of semicircular canal manipulation. Generally, perilymph leak was found to cause a slight hearing loss that was predominately recovered during surgery. However, transaction of the membranous labyrinth usually caused a more significant hearing loss that was not recovered during the surgery. In addition, the magnitude of hearing loss seemed to be increased with the elongation of the surgery. However, the hearing can be largely recovered after the surgery even in animals with transaction of the membranous labyrinth. Conclusion: Hearing loss caused by TSCO can be greatly reduced by avoiding damage to the membranous labyrinth and by shortening the operation time.