Maintenance of delay-period activity in working memory task is modulated by local network structure.

Revealing the relationship between neural network structure and function is one central theme of neuroscience. In the context of working memory (WM), anatomical data suggested that the topological structure of microcircuits within WM gradient network may differ, and the impact of such structural heterogeneity on WM activity remains unknown. Here, we proposed a spiking neural network model that can replicate the fundamental characteristics of WM: delay-period neural activity involves association cortex but not sensory cortex. First, experimentally observed receptor expression gradient along the WM gradient network is reproduced by our network model. Second, by analyzing the correlation between different local structures and duration of WM activity, we demonstrated that small-worldness, excitation-inhibition balance, and cycle structures play crucial roles in sustaining WM-related activity. To elucidate the relationship between the structure and functionality of neural networks, structural circuit gradients in brain should also be subject to further measurement. Finally, combining anatomical data, we simulated the duration of WM activity across different brain regions, its maintenance relies on the interaction between local and distributed networks. Overall, network structural gradient and interaction between local and distributed networks are of great significance for WM.

Vocalization-induced middle ear muscle reflex and auditory fovea do not contribute to the unimpaired auditory sensitivity after intense noise exposure in the CF-FM bat, Hipposideros pratti.

Behaviors and auditory physiological responses of some species of echolocating bats remain unaffected after exposure to intense noise, but information on the underlying mechanisms remains limited. Here, we studied whether the vocalization-induced middle ear muscle (MEM) contractions (MEM reflex) and auditory fovea contributed to the unimpaired auditory sensitivity of constant frequency-frequency modulation (CF-FM) bats after exposure to broad-band intense noise. The vocalizations of the CF-FM bat, Hipposideros pratti, were inhibited through anesthesia to eliminate the vocalization-induced MEM reflex. First, the anesthetized bats were exposed to intense broad-band noise, and the findings showed that the bats could still maintain their auditory sensitivities. However, auditory sensitivities were seriously impaired in CBA/Ca mice exposed to intense noise under anesthesia. This indicated that the unimpaired auditory sensitivity in H. pratti after exposure to intense noise under anesthesia was not due to anesthetization. The bats were further exposed to low-frequency band-limited noise, whose passband did not overlap with echolocation call frequencies. The results showed that the auditory responses to sound frequencies within the noise spectrum and one-half octave higher than the spectrum were also unimpaired. Taken together, the results indicate that both vocalization-induced MEM reflex and auditory fovea do not contribute to the unimpaired auditory sensitivity in H. pratti after exposure to intense noise. The possible mechanisms underlying the unimpaired auditory sensitivity after echolocating bats were exposed to intense noise are discussed.

[Noise exposure-induced stress response and its measurement methods].

Noise, as an unavoidable stress (pressure) source in the modern life, affects animals in many ways, both behaviorally and physiologically. Behavioral changes may be driven by changes in hormone secretion in animals. When animals face with noise stress, the neuroendocrine systems, mainly the hypothalamic-pituitary-adrenal (HPA) axis, are activated, which promotes the secretion and release of stress hormones, and then leads to a series of behavioral changes. The behavioral changes can be easily observed, but the changes in physiological indicators such as hormone levels need to be accurately measured. Currently, many studies have measured the variations of stress hormone levels in animals under different noise conditions. Taking glucocorticoid as an example, this paper summarizes the different measurement methods of stress hormones, especially the non-invasive measurement methods, and compares the advantages and shortcomings of them. It provides a variety of measurement choices for the study of related issues, and also helps us to further understand the sources of animal stress, in order to provide a better habitat for animals.

[Research progress of the regulation of cochlear sensitivity to noise by circadian rhythm].

High level noise can damage cochlear hair cells, auditory nerve and synaptic connections between cochlear hair cells and auditory nerve, resulting in noise-induced hearing loss (NIHL). Recent studies have shown that animal cochleae have circadian rhythm, which makes them different in sensitivity to noise throughout the day. Cochlear circadian rhythm has a certain relationship with brain-derived neurotrophic factor and glucocorticoids, which affects the degree of hearing loss after exposure to noise. In this review, we summarize the research progress of the regulation of cochlear sensitivity to noise by circadian rhythm and prospect the future research direction.

Investigation of Neuron Latency Modulated by Bilateral Inferior Collicular Interactions Using Whole-Cell Patch Clamp Recording in Brain Slices.

As the final level of the binaural integration center in the subcortical nucleus, the inferior colliculus (IC) plays an essential role in receiving binaural information input. Previous studies have focused on how interactions between the bilateral IC affect the firing rate of IC neurons. However, little is known concerning how the interactions within the bilateral IC affect neuron latency. In this study, we explored the synaptic mechanism of the effect of bilateral IC interactions on the latency of IC neurons. We used whole-cell patch clamp recordings to assess synaptic responses in isolated brain slices of Kunming mice. The results demonstrated that the excitation-inhibition projection was the main projection between the bilateral IC. Also, the bilateral IC interactions could change the reaction latency of most neurons to different degrees. The variation in latency was related to the type of synaptic input and the relative intensity of the excitation and inhibition. Furthermore, the latency variation also was caused by the duration change of the first subthreshold depolarization firing response of the neurons. The distribution characteristics of the different types of synaptic input also differed. Excitatory-inhibitory neurons were widely distributed in the IC dorsal and central nuclei, while excitatory neurons were relatively concentrated in these two nuclei. Inhibitory neurons did not exhibit any apparent distribution trend due to the small number of assessed neurons. These results provided an experimental reference to reveal the modulatory functions of bilateral IC projections.

Evoked potential study of the inferior collicular response to constant frequency-frequency modulation (CF-FM) sounds in FM and CF-FM bats.

The auditory system of echolocating bats is adapted for processing species-specific ultrasonic signals. While FM (frequency modulation) bats are strictly sensitive to the frequency ranges of their orientation signals or prey-generated noise, CF-FM (constant frequency-FM) bats have a disproportionate number of neurons tuned to frequencies near the CF component of their orientation sounds, and most of them are on-off responders. Furthermore, the inferior collicular neurons of the CF-FM bats discharged as single-on or double-on responders to CF-FM stimuli. To further study the differences in auditory signal processing of these two types of bats, as the first step we conducted an evoked potential response study in the inferior colliculus of the CF-FM bat, Hipposideros pratti and the FM bat, Pipistrellus abramus using CF, FM and CF-FM stimuli. The results showed that the CF sounds always evoked collicular on- and off-responses in CF-FM bats, but the FM bats only had on-responses to both CF and FM sounds, indicting species-specific neural circuits. However, when stimulated with CF-FM sounds, collicular responses were evoked by both the CF and FM components from both FM and CF-FM bats, suggesting they have some generic neural circuit.

Amplitude- and duration-sensitivity of single-on and double-on neurons to CF-FM stimuli in inferior colliculus of Pratt's roundleaf bat (Hipposideros pratti).

During hunting, the duration and amplitude of bat's echolocation sounds co-vary. Our previous studies showed the inferior collicular neurons of constant frequency-frequency modulation (CF-FM) bat discharged as single-on (SO) or double-on (DO) responders when stimulated with behavior related CF-FM sounds. However, how the co-varied sound duration and amplitude modulate the response properties of SO and DO neurons were understudied. Therefore, we investigated amplitude- and duration-sensitivity in 121 neurons isolated in the inferior colliculus of CF-FM bat, Pratt's roundleaf bat (Hipposideros pratti). Responses of SO and DO neurons were obtained by in vivo intracellular recordings and examined for different stimulus amplitudes and durations. Our results revealed that response patterns of SO neurons were unaffected by changes in amplitude and duration of CF-FM stimuli. However, the excitability of DO neurons increased with prolonged CF duration and higher amplitude of CF-FM stimuli. These data suggested that the invariance of SO neurons play a key role in detection of Doppler shift and glint-like changes of frequency and amplitude induced by wingbeats of insects. In contrast, amplitude- and duration-sensitivity of DO neurons to CF-FM stimuli is consistent with the systematic changes in these signal parameters during sequential phases of foraging in CF-FM bats.

Plastic Change in the Auditory Minimum Threshold Induced by Intercollicular Effects in Mice.

In the auditory pathway, the commissure of the inferior colliculus (IC) interconnects the two ICs on both sides of the dorsal midbrain. This interconnection could mediate an interaction between the two ICs during sound signal processing. The intercollicular effects evoked by focal electric stimulation for 30 min could inhibit or facilitate auditory responses and induce plastic changes in the response minimum threshold (MT) of IC neurons. Changes in MT are dependent on the best frequency (BF) and MT difference. The MT shift is larger in IC neurons with BF differences ≤2 kHz than in those with BF differences >2 kHz. Moreover, MTs that shift toward electrically stimulated IC neurons increase with the increasing MT difference between the two ICs. The shift in MT lasts for a certain period of time and then returns to previous levels within ~150 min. The collicular interactions are either reciprocal or unilateral under alternate stimulating and recording conditions in both ICs. Our results suggest that intercollicular effects may be involved in the acoustic experience-dependent plasticity of the MT of IC neurons.

Effect of echolocation behavior-related constant frequency-frequency modulation sound on the frequency tuning of inferior collicular neurons in Hipposideros armiger.

In constant frequency-frequency modulation (CF-FM) bats, the CF-FM echolocation signals include both CF and FM components, yet the role of such complex acoustic signals in frequency resolution by bats remains unknown. Using CF and CF-FM echolocation signals as acoustic stimuli, the responses of inferior collicular (IC) neurons of Hipposideros armiger were obtained by extracellular recordings. We tested the effect of preceding CF or CF-FM sounds on the shape of the frequency tuning curves (FTCs) of IC neurons. Results showed that both CF-FM and CF sounds reduced the number of FTCs with tailed lower-frequency-side of IC neurons. However, more IC neurons experienced such conversion after adding CF-FM sound compared with CF sound. We also found that the Q 20 value of the FTC of IC neurons experienced the largest increase with the addition of CF-FM sound. Moreover, only CF-FM sound could cause an increase in the slope of the neurons' FTCs, and such increase occurred mainly in the lower-frequency edge. These results suggested that CF-FM sound could increase the accuracy of frequency analysis of echo and cut-off low-frequency elements from the habitat of bats more than CF sound.

[Research progress in neurophysiological mechanism underlying distinguishing plants through classification of echoes in frequency modulation bats].

By using echolocation system echolocating bats have the ability to complete the tasks of detection, localization and classification of the targets. Among the three fundamental tasks, the study of how bats use echolocation to classify targets was investigated later, and most of previous studies were focused on the analysis of simple targets. However, the echoes that bats received are mostly returning from complex objects or structures, which are so complex that they must be described by stochastic statistical approach. In recent years, the study on classification of complex echoes returning from different plants in frequency modulation (FM) bats has made significant progress. In this review article, we will briefly introduce and comment on some progress of studies based on the behavioral evidence, acoustic cues, relevant classification models, and neural bases underlying different classification cues to distinguish plants through classification of echoes in FM bats.

[Relation between frequency modulation direction selectivity and forward masking of inferior collicular neurons: a study on in vivo intracellular recording in mice].

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.

Background noise responding neurons in the inferior colliculus of the CF-FM bat, Hipposideros pratti.

The Lombard effect, referring to an involuntary rise in vocal intensity, is a widespread vertebrate mechanism that aims to maintain signal efficiency in response to ambient noise. Previous studies showed that the Lombard effect could be sufficiently implemented at subcortical levels and operated by continuously monitoring background noise, requiring some subcortical auditory sensitive neurons to have continuous responses to background noise. However, such neurons have not been well characterized. The inferior colliculus (IC) is a major auditory integration center under the auditory cortex and provides projections to the putative vocal pattern generator in the brainstem. Thus, it is reasonable to speculate that the IC is a likely auditory nucleus candidate having background noise responding neurons (BNR neurons). In the present study, we isolated 183 sound-sensitive IC neurons in a constant frequency-frequency modulation bat, Hipposideros pratti, and found that around 19% of these IC neurons are BNR neurons when stimulated with 70 dB SPL background white noise. Their firing rates in response to noise increased with increasing noise intensity and could be suppressed by sound stimulation. Furthermore, compared to neurons with similar best frequencies, the BNR neurons had smaller Q10-dB values and lower noise-induced minimal threshold change, indicating that BNR neurons received fewer inhibitory inputs. These results suggested that the BNR neurons are ideal candidates for collecting information about background noise. We proposed that the BNR neurons synapsed with neurons in vocal-pattern-generating networks in the brainstem and initiated the Lombard effect by a feed-forward loop.

Spectrally non-overlapping background noise disturbs echolocation via acoustic masking in the CF-FM bat, Hipposideros pratti.

The environment noise may disturb animal behavior and echolocation via three potential mechanisms: acoustic masking, reduced attention and noise avoidance. Compared with the mechanisms of reduced attention and noise avoidance, acoustic masking is thought to occur only when the signal and background noise overlap spectrally and temporally. In this study, we investigated the effects of spectrally non-overlapping noise on echolocation pulses and electrophysiological responses of a constant frequency-frequency modulation (CF-FM) bat, Hipposideros pratti. We found that H. pratti called at higher intensities while keeping the CFs of their echolocation pulses consistent. Electrophysiological tests indicated that the noise could decrease auditory sensitivity and sharp intensity tuning, suggesting that spectrally non-overlapping noise imparts an acoustic masking effect. Because anthropogenic noises are usually concentrated at low frequencies and are spectrally non-overlapping with the bat's echolocation pulses, our results provide further evidence of negative consequences of anthropogenic noise. On this basis, we sound a warning against noise in the foraging habitats of echolocating bats.

Constant Resting Frequency and Auditory Midbrain Neuronal Frequency Analysis of Hipposideros pratti in Background White Noise.

Acoustic communication signals are inevitably challenged by ambient noise. In response to noise, many animals adjust their calls to maintain signal detectability. However, the mechanisms by which the auditory system adapts to the adjusted pulses are unclear. Our previous study revealed that the echolocating bat, Hipposideros pratti, increased its pulse intensity in the presence of background white noise. In vivo single-neuron recording demonstrated that the auditory midbrain neurons tuned to the second harmonic (H2 neurons) increased their minimal threshold (MT) to a similar degree as the increment of pulse intensity in the presence of the background noise. Furthermore, the H2 neurons exhibited consistent spike rates at their best amplitudes and sharper intensity tuning with background white noise compared with silent conditions. The previous data indicated that sound intensity analysis by auditory midbrain neurons was adapted to the increased pulse intensity in the same noise condition. This study further examined the echolocation pulse frequency and frequency analysis of auditory midbrain neurons with noise conditions. The data revealed that H. pratti did not shift the resting frequency in the presence of background noise. The auditory midbrain neuronal frequency analysis highly linked to processing the resting frequency with the presence of noise by presenting the constant best frequency (BF), frequency sensitivity, and frequency selectivity. Thus, our results suggested that auditory midbrain neuronal responses in background white noise are adapted to process echolocation pulses in the noise conditions.

The second harmonic neurons in auditory midbrain of Hipposideros pratti are more tolerant to background white noise.

Although acoustic communication is inevitably influenced by noise, behaviorally relevant sounds are perceived reliably. The noise-tolerant and -invariant responses of auditory neurons are thought to be the underlying mechanism. So, it is reasonable to speculate that neurons with best frequency tuned to behaviorally relevant sounds will play important role in noise-tolerant perception. Echolocating bats live in groups and emit multiple harmonic signals and analyze the returning echoes to extract information about the target features, making them prone to deal with noise in their natural habitat. The echolocation signal of Hipposideros pratti usually contains 3-4 harmonics (H1H4), the second harmonic has the highest amplitude and is thought to play an essential role during echolocation behavior. Therefore, it is reasonable to propose that neurons tuned to the H2, named the H2 neurons, can be more noise-tolerant to background noise. Taking advantage of bat's stereotypical echolocation signal and single-cell recording, our present study showed that the minimal threshold increases (12.2 dB) of H2 neurons in the auditory midbrain were comparable to increase in bat's call intensity (14.2 dB) observed in 70 dB SPL white noise condition, indicating that the H2 neurons could work as background noise monitor. The H2 neurons had higher minimal thresholds and sharper frequency tuning, which enabled them to be more tolerant to background noise. Furthermore, the H2 neurons had consistent best amplitude spikes and sharper intensity tuning in background white noise condition than in silence. Taken together, these results suggest that the H2 neurons might account for noise-tolerant perception of behaviorally relevant sounds.

[Sound duration and sound pattern affect the recovery cycles of inferior collicular neurons in leaf-nosed bat, Hipposideros armiger].

The effects of sound duration and sound pattern on the recovery cycles of inferior collicular (IC) neurons in constant frequency-frequency modulation (CF-FM) bats were explored in this study. Five leaf-nosed bats, Hipposideros armiger (4 males, 1 female, 43-50 g body weight), were used as subjects. The extracellular responses of IC neurons to paired sound stimuli with different duration and patterns were recorded, and the recovery was counted as the ratio of the second response to the first response. Totally, 169 sound-sensitive IC neurons were recorded in the experiment. According to the interpulse interval (IPI) of paired sounds when neurons reached 50% recovery (50% IPI), the recovery cycles of these IC neurons were classified into 3 types: fast recovery (F, the 50% IPI was less than 15 ms), short recovery (S, the 50% IPI was between 15.1 and 30 ms) and long recovery (L, the 50% IPI was more than 30 ms). When paired CF stimuli with 2 ms duration was used, the ratio of F neurons was 32.3%, and it decreased to 18.1% and 18.2% respectively when 5 and 7 ms CF stimuli were used. The ratios of S and L neurons were 41.5%, 33.7%, 29.1% and 26.2%, 48.2%, 52.7% respectively when 2, 5 and 7 ms CF stimuli were used. The average 50% IPI determined after stimulation with paired 2 ms, 5 ms and 7 ms CF sounds were (30.2 ± 27.6), (39.9 ± 29.1) and (49.4 ± 34.7) ms, respectively, and the difference among them was significant (P< 0.01). When the stimuli of paired 2 ms CF sounds were shifted to paired 2 ms FM sounds, the proportion of F, S and L neurons changed from 32.3%, 41.5%, 26.2% to 47.7%, 24.6%, 27.7%, respectively, and the average 50% IPI decreased from (30.2 ± 27.6) to (23.9 ± 19.0) ms (P< 0.05, n = 65). When paired 5+2 ms CF-FM pulses were used instead of 7 ms CF sounds, the proportion of F, S and L neurons changed from 18.2%, 29.1%, 52.7% to 29.1%, 27.3%, 43.6%, respectively, and the average 50% IPI decreased from (49.4 ± 34.7) to (36.3 ± 29.4) ms (P< 0.05, n = 55). All these results suggest that the CF and FM components in echolocation signal of CF-FM bats play different roles during bats' hunting and preying on. The FM component of CF-FM signal presenting in the terminal phase can increase the number of F type neurons and decrease the recovery cycles of IC neurons for processing high repetition echo information, which ensures the bat to analyze the target range and surface texture more accurately.

TRPM5-expressing Microvillous Cells Regulate Region-specific Cell Proliferation and Apoptosis During Chemical Exposure.

The mammalian main olfactory epithelium (MOE) is exposed to a wide spectrum of external chemicals during respiration and relies on adaptive plasticity to maintain its structural and functional integrity. We previously reported that the chemo-responsive and cholinergic transient receptor potential channel M5 (TRPM5)-expressing-microvillous cells (MCs) in the MOE are required for maintaining odor-evoked electrophysiological responses and olfactory-guided behavior during two-week exposure to an inhaled chemical mixture. Here, we investigated the underlying factors by assessing the potential modulatory effects of TRPM5-MCs on MOE morphology and cell proliferation and apoptosis, which are important for MOE maintenance. In the posterior MOE of TRPM5-GFP mice, we found that two-week chemical exposure induced a significant increase in Ki67-expressing proliferating basal stem cells without a significant reduction in the thickness of the whole epithelium or mature olfactory sensory neuron (OSN) layer. This adaptive increase in stem cell proliferation was missing in chemical-exposed transcription factor Skn-1a knockout (Skn-1a-/-) mice lacking TRPM5-MCs. In addition, a greater number of isolated OSNs from chemical-exposed Skn-1a-/- mice displayed unhealthily high levels of resting intracellular Ca2+. Intriguingly, in the anterior MOE where we found a higher density of TRPM5-MCs, chemical-exposed TRPM5-GFP mice exhibited a time-dependent increase in apoptosis and a loss of mature OSNs without a significant increase in proliferation or neurogenesis to compensate for OSN loss. Together, our data suggest that TRPM5-MC-dependent region-specific upregulation of cell proliferation in the majority of the MOE during chemical exposure contributes to the adaptive maintenance of OSNs and olfactory function.

Behaviorally relevant frequency selectivity in single- and double-on neurons in the inferior colliculus of the Pratt's roundleaf bat, Hipposideros pratti.

Frequency analysis is a fundamental function of the auditory system, and it is essential to study the auditory response properties using behavior-related sounds. Our previous study has shown that the inferior collicular (IC) neurons of CF-FM (constant frequency-frequency modulation) bats could be classified into single-on (SO) and double-on (DO) neurons under CF-FM stimulation. Here, we employed Pratt's roundleaf bats, Hipposideros pratti, to investigate the frequency selectivity of SO and DO neurons in response to CF and behavior-related CF-FM sounds using in vivo extracellular recordings. The results demonstrated that the bandwidths (BWs) of iso-frequency tuning curves had no significant differences between the SO and the DO neurons when stimulated by CF sounds. However, the SO neurons had significant narrower BWs than DO neurons when stimulated with CF-FM sounds. In vivo intracellular recordings showed that both SO and DO neurons had significantly shorter post-spike hyperpolarization latency and excitatory duration in response to CF-FM in comparison to CF stimuli, suggesting that the FM component had an inhibitory effect on the responses to the CF component. These results suggested that SO neurons had higher frequency selectivity than DO neurons under behavior-related CF-FM stimulation, making them suitable for detecting frequency changes during echolocation.

ATP and Odor Mixture Activate TRPM5-Expressing Microvillous Cells and Potentially Induce Acetylcholine Release to Enhance Supporting Cell Endocytosis in Mouse Main Olfactory Epithelium.

The main olfactory epithelium (MOE) functions to detect odor molecules, provide an epithelial surface barrier, and remove xenobiotics from inhaled air. Mechanisms coordinating the activities of different cell types within the MOE to maintain these functions are poorly understood. Previously, we showed that superficially located microvillous cells (MCs) in the MOE expressing transient receptor potential channel M5 (TRPM5) are cholinergic and chemoresponsive and that they play an important role in maintaining odor responses and olfactory-guided behavior under challenging chemical environment. Here we investigated TRPM5-MC activation and subsequent paracrine regulation. Ca2+ imaging showed that TRPM5-MCs dose-dependently increase their intracellular Ca2+ levels in response to ATP, an important signaling molecule for airway mucociliary movement, and to an odor mixture. Pharmacological examination showed that the ATP responses are primarily mediated by P2X purinergic receptors. Interestingly, using the endocytosis dye pHrodo Red dextran, we found that chemical-activated TRPM5-MCs significantly increase the number of pHrodo-labeled puncta compared to controls without stimulation and compared to cells that do not respond to ATP or to the odor mixture. These results indicate potential vesicle recycling after release of the signaling molecule acetylcholine (ACh). Interestingly, TRPM5 knockout (KO) results in a decrease in ATP-induced pHrodo internalization. We further investigated cholinergic regulation of neighboring supporting cells (SCs). We found that ACh strongly elevates intracellular Ca2+ and potentiates pHrodo endocytosis in SCs. The ACh effects are diminished in the presence of atropine or M3 muscarinic receptor antagonist and in SCs lacking M3 receptors. Collectively, these data suggest that TRPM5-MCs may regulate the MOE's multicellular network activity via cholinergic paracrine signaling for functional maintenance and adaptive plasticity.

Association of the C47T polymorphism in superoxide dismutase gene 2 with noise-induced hearing loss: a meta-analysis.

INTRODUCTION: Currently, there is limited information about the relationship between manganese superoxide dismutase (sod2) c47t polymorphism and susceptibility to noise-induced hearing loss (NIHL). OBJECTIVE: The aim of this meta-analysis was to clarify the association between SOD2 C47T polymorphism and NIHL. METHODS: A search in PubMed and Web of Science was performed to collect data. All full-text, English-written studies containing sufficient and complete case-and-control data about the relationship between SOD2 C47T polymorphism and NIHL were included. Three eligible studies, comprising 1094 subjects, were identified. pooled odds ratios (ORs) and 95% confidence intervals (CI) were calculated to evaluate the strength of the association between SOD2 C47T polymorphism and NIHL. RESULTS: No significant association between C47T polymorphism and risk of NIHL was found with the following combinations: T vs. C (OR=0.83; 95% CI=0.63-1.09); TT vs. CC (OR=0.49; 95% CI=0.22-1.09); CT vs. CC (OR=0.54; 95% CI=0.25-1.17); TT vs. CC+CT (OR=0.82; 95% CI=0.50-1.32); CC vs. TT+TC (OR=0.49; 95% CI=0.23-1.04). However, in subgroup analysis, a significant association was found for TT vs. CC+CT (OR=0.77; 95% CI=0.42-1.41) in the Chinese population. CONCLUSION: The present meta-analysis suggests that SOD2 C47T polymorphism is significantly associated with increased risk of NIHL in the Chinese population. Further large and well-designed studies are needed to confirm this association.