OBJECTIVES.: Sodium salicylate (SS) is well known for its ototoxic properties that induce functional and morphological changes in the cochlea and brain. Ginkgo biloba extract (GBE) has been widely used for treatment of various neurodegenerative diseases; however, its effects on salicylate-induced ototoxicity remain unclear. Herein, we examined the effects of EGb 761 (EGb), a standard form of GBE, on the plasticity of the N-methyl-D-aspartate receptor subunit 2B (GluN2B) in the inferior colliculus (IC) following SS administration. METHODS.: Seven-week-old Sprague Dawley rats (n=24) were randomly allocated to control, SS, EGb, and EGb+SS groups. The SS group received a single intraperitoneal SS injection (350 mg/kg), the EGb group received EGb orally for 5 consecutive days (40 mg/kg), and the EGb+SS group received EGb for 5 consecutive days, followed by an SS injection. The auditory brainstem responses (ABRs) were assessed at baseline and 2 hours after SS administration. GluN2B expression was examined by Western blot and immunohistochemistry. RESULTS.: There were no significant differences in ABR threshold shifts among the groups. The expression of the GluN2B protein normalized by which of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was significantly lower in the EGb+SS group, as compared to the SS group (P=0.012). Weak and diffused GluN2B immunoreactivity was detected in the IC neural cells of the EGb+SS group, while those of the SS group exhibited strong and diffused GluN2B positivity. CONCLUSION.: EGb may play a role in regulating the GluN2B expression in the IC of salicylate-induced ototoxicity model.
Blotting, Western ; Brain ; Cochlea ; Evoked Potentials, Auditory, Brain Stem ; Ginkgo biloba ; Glyceraldehyde 3-Phosphate ; Immunohistochemistry ; Inferior Colliculi ; N-Methylaspartate ; Neurodegenerative Diseases ; Oxidoreductases ; Plastics ; Rats, Sprague-Dawley ; Sodium Salicylate

Wernicke encephalopathy is a syndrome caused by thiamine deficiency whose three typical symptoms are ophthalomoplegia, ataxia, and confusion. There are also rare reports of bilateral hearing loss, which can be caused by damage to the bilateral inferior colliculus or thalamic lesions, or by energy failure of the cochlea. This case suggests that thiamine should be administered based on the possibility of Wernicke encephalopathy occurring in malnourished or alcoholic patients with sudden bilateral hearing loss.
Alcoholics ; Ataxia ; Cochlea ; Hearing Loss ; Hearing Loss, Bilateral ; Humans ; Inferior Colliculi ; Thiamine ; Thiamine Deficiency ; Wernicke Encephalopathy

The circling mice with tmie gene mutation are known as an animal deafness model, which showed hyperactive circling movement. Recently, the reinvestigation of circling mouse was performed to check the inner ear pathology as a main lesion of early hearing loss. In this trial, the inner ear organs were not so damaged to cause the hearing deficit of circling (cir/cir) mouse at 18 postnatal day (P18) though auditory brainstem response data indicated hearing loss of cir/cir mice at P18. Thus, another mechanism may be correlated with the early hearing loss of cir/cir mice at P18. Hearing loss in the early life can disrupt the ascending and descending information to inferior colliculus (IC) as integration site. There were many reports that hearing loss could result in the changes in Ca²⁺ concentration by either cochlear ablation or genetic defect. However, little was known to be reported about the correlation between the pathology of IC and Ca²⁺ changes in circling mice. Therefore, the present study investigated the distribution of calcium-binding proteins (CaBPs), calbindin-D28k, parvalbumin, and calretinin immunoreactivity (IR) in the IC to compare among wild-type (+/+), heterozygous (+/cir), and homozygous (cir/cir) mice by immunohistochemistry. The decreases of CaBPs IR in cir/cir were statistically significant in the neurons as well as neuropil of IC. Thus, this study proposed overall distributional alteration of CaBPs IR in the IC caused by early hearing defect and might be helpful to elucidate the pathology of central auditory disorder related with Ca²⁺ metabolism.
Animals ; Calbindin 1* ; Calbindin 2* ; Calcium-Binding Proteins ; Deafness ; Ear, Inner ; Evoked Potentials, Auditory, Brain Stem ; Hearing ; Hearing Loss ; Immunohistochemistry ; Inferior Colliculi* ; Metabolism ; Mice* ; Neurons ; Neuropil ; Parvalbumins ; Pathology

OBJECTIVETo observe the expressions of Calbindin(CB) and Parvalbumin (PV), the two calcium-binding protein, in auditory pathway in mice of wild type C57BL/6J and kit⁺/kitW⁻ ²Bao, a kit gene mutant.

METHODSSix mutated kit gene kit⁺/kitW⁻ ²Bao mice and 6 wild type C57BL/6J (B6) mice were anaesthetized i. p. with chloral hydrate. After the mice were fixed by heart perfusion, the brains were removed and coronal sections were cut with a freezing microtome.

RESULTSWe found that wild type mice had significant expressions of PV on ventral cochlear nucleus, anterior part (AVCN), ventral cochlear nucleus, posterior part (PVCN), inferior colliculus (IC) and auditory cortex (AC). CB was expressed in wild type mice on PVCN and nucleus of the trapezoid body (Tz). The mutant of kit gene induced the less expression of PV on PVCN, IC and AC (P < 0.01), but increased the expression of Tz (P < 0.01). CB could not be observed on PVCN in mutant mice, and the expression of AC was increased( P < 0.01).

CONCLUSIONCB and PV has differential expression level in auditory pathway. Since mutated kit gene can affect expression of PV on PVCN, IC, Tz and AC, as well as CB on PVCN and AC, it suggests that the mutation of kit gene can affect the advanced function of central nervous system in auditory pathway.

Animals ; Auditory Cortex ; metabolism ; Auditory Pathways ; metabolism ; Calbindins ; metabolism ; Inferior Colliculi ; metabolism ; Mice ; Mice, Inbred C57BL ; Mutation ; Parvalbumins ; metabolism ; Pons ; metabolism ; Proto-Oncogene Proteins c-kit ; genetics

OBJECTIVETo explore the effects of electrical stimulation at acupoints in the distribution area of auricular vagus nerve combined with sound masking on auditory brainstem response (ABR) and contents of neurotransmitters of γ-aminobutyric acid (γ-GABA), 5-hydroxytryptamine (5-HT) and acetyl choline (Ach) in inferior colliculus of tinnitus rats.

METHODSTwenty-four male adult SD rats were randomized into a control group, a model group, a 7-d treatment group and a 15-d treatment group. Except the control group, rats in the remaining groups were treated with intraperitoneal injection of 10% salicylate sodium at a dose of 350 mg/kg to establish tinnitus model. Rats in the control group were treated with injection of 0.9% NaCl. Rats in the 7-d treatment group and 15-d treatment group were treated with electrical stimulation at "Shenmen (TF₄)" and "Yidan (CO₁₁)" in the distribution area of auricular vagus nerve combined with sound masking, once a day, for 7 days and 15 days. The SigGenRP software of TDT system was applied to provide voice for single ear and collect the signal, and the voice threshold of ABR was tested. The levels of γ-GABA, 5-HT and Ach in inferior colliculus of rats were detected by enzyme linked immunosorbent assay (ELISA) and compared.

RESULTSCompared with the model group, the threshold values of ABR in 12 kHz and 16 kHz voice stimulation in the 7-d treatment group were significantly lower all P < 0.05); the threshold values of ABR from 4 kHz to 28 kHz voice stimulation in the 15-d treatment group were signally reduced (P < 0.05, P < 0.01), which was more significant than those in the 7-d treatment group. The level of γ-GABA in the model group was significantly lower than that in the control group (P < 0.05), and that in the 15-d treatment group was apparently higher than that in the model group (P < 0.05). The level of 5-HT in the model group was markedly higher than that in the control group (P < 0.05), and that in the 7-d treatment group was lower than that in the model group (P < 0.05), while that in the 15-d treatment group was apparently higher than that in the model group (P < 0.05). The level of Ach in the model group was obviously; lower than that in the control group (P < 0.05), and that in the 7-d treatment group was higher than that in the model group (P < 0.05).

CONCLUSIONElectrical stimulation at auricular vagus nerve combined with sound masking) could regulate the threshold of ABR, especially in the 15-d treatment group. This may be ascribed to modulating the levels of neurotransmitter of γ-GABA, 5-HT and Ach in inferior colliculus.

Acupuncture Points ; Animals ; Brain Stem ; physiopathology ; Electric Stimulation ; Evoked Potentials, Auditory, Brain Stem ; Humans ; Inferior Colliculi ; physiopathology ; Male ; Neurotransmitter Agents ; metabolism ; Rats ; Rats, Sprague-Dawley ; Serotonin ; metabolism ; Tinnitus ; physiopathology ; therapy ; Vagus Nerve ; physiopathology ; gamma-Aminobutyric Acid ; metabolism

The dorsal nucleus of lateral lemniscus (DNLL) is a nucleus in the auditory ascending pathway, and casts inhibitory efferent projections to the inferior colliculus. Studies on the DNLL are less than studies on the auditory brain stem and inferior colliculus. To date, there is no information about response characteristics of neurons in DNLL of albino mouse. Under free field conditions, we used extracellular single unit recording to study the acoustic signal characteristics of DNLL neurons in Kunming mice (Mus musculus). Transient (36%) and ongoing (64%) firing patterns were found in 96 DNLL neurons. Neurons with different firing patterns have significant differences in characteristic frequency and minimal threshold. We recorded frequency tuning curves (FTCs) of 87 DNLL neurons. All of the FTCs exhibit an open "V" shape. There is no significant difference in FTCs between transient and ongoing neurons, but among the ongoing neurons, the FTCs of sustained neurons are sharper than those of onset plus sustained neurons and pauser neurons. Our results showed that the characteristic frequency of DNLL neurons of mice was not correlated with depth, supporting the view that the DNLL of mouse has no frequency topological organization through dorsal-ventral plane, which is different from cats and some other animals. Furthermore, by using rate-intensity function (RIF) analysis the mouse DNLL neurons can be classified as monotonic (60%), saturated (31%) and non-monotonic (8%) types. Each RIF type includes transient and ongoing firing patterns. Dynamic range of the transient firing pattern is smaller than that of ongoing firing ones (P < 0.01), suggesting that the inhibitory inputs may underlie the formation of transient firing pattern. Multiple firing patterns and intensity coding of DNLL neurons may derive from the projections from multiple auditory nuclei, and play different roles in auditory information processing.
Animals ; Auditory Pathways ; Brain Stem ; Cats ; Inferior Colliculi ; Mice ; Neurons ; Pons

The inferior colliculus (IC) is a pivot along the central auditory pathway. Using infrared visual whole-cell patch clamp recording technique, we investigated the electrophysiological properties of IC subnuclei neurons. Recordings were made from 88 neurons, including 21 neurons from the dorsal cortex of the IC (ICd), 43 neurons from the central nucleus of the IC (ICc) and 24 neurons from the external cortex of the IC (ICx). Based on the responses to positive current injection, three firing patterns, i.e., onset (6.8%, n = 6), adapting (39.8%, n = 35) and sustained (53.4%, n = 47) patterns, were identified. The hyperpolarization-activated inward current (Ih) could be recorded in half of the neurons (49/88). The sustained pattern occurred in more than half of ICd and ICc neurons (61.9% and 67.4%), while the adapting pattern occurred in majority of ICx neurons (75%). Action potential (AP) threshold and time constant also showed significant differences across neurons from the ICd, the ICc and the ICx. Our results indicate that IC neurons are different in electrophysiological properties across the subnuclei. The variance of the responses may be related to the distinct types of neurons as well as the received projections, which is implicated in the distinct roles of IC neurons in central auditory processing.
Action Potentials ; Animals ; Electrophysiological Phenomena ; In Vitro Techniques ; Inferior Colliculi ; cytology ; Mice ; Neurons ; cytology ; Patch-Clamp Techniques

PURPOSE: Several morphometric studies have been performed to investigate brain abnormalities in congenitally deaf people. But no report exists concerning structural brain abnormalities in congenitally deaf adolescents. We evaluated the regional volume changes in gray matter (GM) using voxel-based morphometry (VBM) in congenitally deaf adolescents. MATERIALS AND METHODS: A VBM8 methodology was applied to the T1-weighted magnetic resonance imaging (MRI) scans of eight congenitally deaf adolescents (mean age, 15.6 years) and nine adolescents with normal hearing. All MRI scans were normalized to a template and then segmented, modulated, and smoothed. Smoothed GM data were tested statistically using analysis of covariance (controlled for age, gender, and intracranial cavity volume). RESULTS: The mean values of age, gender, total volumes of GM, and total intracranial volume did not differ between the two groups. In the auditory centers, the left anterior Heschl's gyrus and both inferior colliculi showed decreased regional GM volume in the congenitally deaf adolescents. The GM volumes of the lingual gyri, nuclei accumbens, and left posterior thalamic reticular nucleus in the midbrain were also decreased. CONCLUSIONS: The results of the present study suggest that early deprivation of auditory stimulation in congenitally deaf adolescents might have caused significant underdevelopment of the auditory cortex (left Heschl's gyrus), subcortical auditory structures (inferior colliculi), auditory gain controllers (nucleus accumbens and thalamic reticular nucleus), and multisensory integration areas (inferior colliculi and lingual gyri). These defects might be related to the absence of general auditory perception, the auditory gating system of thalamocortical transmission, and failure in the maturation of the auditory-to-limbic connection and the auditorysomatosensory-visual interconnection.
Acoustic Stimulation ; Adolescent* ; Auditory Cortex ; Auditory Perception ; Brain ; Hearing ; Humans ; Inferior Colliculi ; Magnetic Resonance Imaging ; Mesencephalon

OBJECTIVE: To investigate the relationship between pure-tone average (PTA), the fractional anisotropy (FA) of the auditory pathway, cognitive cortex and auditory cortex in presbycusis. METHOD: Twenty-five elderly subjects with presbycusis were participated in the study. PTA, speech discrimination abilities were evaluated in each subject. Diffusion tensor imaging (DTI) was applied to access the FA of the IC, the superior frontal gyrus and the Heschl's gyrus. Compare the difference between two sides of the values of FA in the three areas. Bivariate correlation analysis was performed to evaluate the effects of PTA and FA of the inferior colliculus (IC), the superior frontal gyrus and the Heschl's gyrus on speech discrimination abilities. RESULT: There were no significant differences between the left and right side of the inferior colliculus (P > 0.05). Higher FA values were recorded at the left side of the Heschl's gyrus and the superior frontal gyrus (P < 0.05). Both PTA and the FA of the superior frontal gyrus have a negative association with speech discrimination abilities (P < 0.01, P < 0.05), while the FA of the Heschl's gyrus has a positive association with speech discrimination abilities (P < 0.05). CONCLUSION Our findings indicated that the speech discrimination abilities of the elderly is not only related to the peripheral auditory function, but also to the central auditory and cognitive function.
Aged ; Audiometry, Pure-Tone ; Auditory Cortex ; physiopathology ; Auditory Pathways ; Diffusion Tensor Imaging ; Humans ; Inferior Colliculi ; physiopathology ; Presbycusis ; diagnosis ; Speech Perception

It has been reported that the frequency modulation (FM) or FM direction sensitivity and forward masking of central auditory neurons are related with the neural inhibition, but there are some arguments, because no direct evidence of inhibitory synaptic input was obtained in previous studies using extracellular recording. In the present study, we studied the relation between FM direction sensitivity and forward masking of the inferior collicular (IC) neurons using in vivo intracellular recordings in 20 Mus musculus Km mice. Thirty seven with complete data among 93 neurons were analyzed and discussed. There was an inhibitory area which consisted of inhibitory postsynaptic potentials (IPSP) at high frequency side of frequency tuning of up-sweep FM (FMU) sensitive neurons (n = 12) and at low frequency side of frequency tuning of down-sweep FM (FMD) selective neurons (n = 8), while there was no any inhibitory area at both sides of frequency tuning of non-FM sweep direction (FMN) sensitive neurons (n = 17). Therefore, these results show that the inhibitory area at low or high frequency side of frequency tuning is one of the mechanisms for forming FM sweep direction sensitivity of IC neurons. By comparison of forward masking produced by FMU and FMD sound stimuli in FMU, FMD and FMN neurons, the selective FM sounds could produce stronger forward masking than the non-selective in FMU and FMD neurons, while there was no forward masking difference between FMU and FMD stimuli in the FMN neurons. We suggest that the post-action potential IPSP is a potential mechanism for producing stronger forward masking in FMU and FMD neurons.
Acoustic Stimulation ; Action Potentials ; Animals ; Inferior Colliculi ; cytology ; Inhibitory Postsynaptic Potentials ; Mice ; Neurons ; cytology