• Journal of Audiology & Otology
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• v.24 no.3
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• pp.149-156
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• 2020

Background and Objectives: The gap prepulse inhibition of the acoustic startle response has been used to screen tinnitus in an animal model. Here, we examined changes in the auditory late response under various conditions of gap prepulse inhibition. Subjects and Methods: We recruited 19 healthy adults (5 males, 14 females) and their auditory late responses were recorded after various stimuli with or without gap prepulsing. The N1 and P2 responses were selected for analysis. The gap prepulse inhibition was estimated to determine the optimal auditory late response in the gap prepulse paradigm. Results: We found that the gap per se generated a response that was very similar to the response elicited by sound stimuli. This critically affected the gap associated with the maximal inhibition of the stimulus response. Among the various gap-stimulus intervals (GSIs) between the gap and principal stimulus, the GSI of 150 ms maximally inhibited the response. However, after zero padding was used to minimize artifacts after a P2 response to a gap stimulus, the differences among the GSIs disappeared. Conclusions: Overall, the data suggest that both the prepulse inhibition and the gap per se should be considered when using the gap prepulse paradigm to assess tinnitus in humans.

• Korean Journal of Audiology
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• v.24 no.3
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• pp.149-156
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• 2020

Background and Objectives: The gap prepulse inhibition of the acoustic startle response has been used to screen tinnitus in an animal model. Here, we examined changes in the auditory late response under various conditions of gap prepulse inhibition. Subjects and Methods: We recruited 19 healthy adults (5 males, 14 females) and their auditory late responses were recorded after various stimuli with or without gap prepulsing. The N1 and P2 responses were selected for analysis. The gap prepulse inhibition was estimated to determine the optimal auditory late response in the gap prepulse paradigm. Results: We found that the gap per se generated a response that was very similar to the response elicited by sound stimuli. This critically affected the gap associated with the maximal inhibition of the stimulus response. Among the various gap-stimulus intervals (GSIs) between the gap and principal stimulus, the GSI of 150 ms maximally inhibited the response. However, after zero padding was used to minimize artifacts after a P2 response to a gap stimulus, the differences among the GSIs disappeared. Conclusions: Overall, the data suggest that both the prepulse inhibition and the gap per se should be considered when using the gap prepulse paradigm to assess tinnitus in humans.

• Journal of rehabilitation welfare engineering & assistive technology
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• v.7 no.1
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• pp.45-50
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• 2013

Recently, a method for detecting animal tinnitus objectively, gap prepulse inhibition of acoustic startling (GPIAS) were reported. However, the GPIAS method is difficult to be directly applied to human tinnitus research because measuring repeatedly startling responses evoked by more than 110 dB SPL acoustic stimuli for human is not easy. In this paper, the auditory late latency response (ALLR) measurement system which can measure conveniently evoked potentials involving the information about the brain cortical activity related with auditory psychologic phenomena such as a tinnitus has been implemented. By using the implemented system, 8 persons with normal hearing sense have been experimented to measure N1-P2 amplitudes of ALLRs evoked by gap prepulse based acoustic stimuli. Through the experimental results, the prepulse inhibitions of all the participants' N1-P2 responses have been observed and their characteristics were evaluated. And it is verified that our implemented system can be utilized as a device for researching and evaluating the objective tinnitus detection method in the future study.

• Korean Journal of Pharmacognosy
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• v.44 no.2
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• pp.97-103
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• 2013

Schizophrenia is a severe psychiatric disorder and characterized by positive symptom (i.e., delusions, hallucinations), negative symptom (i.e., lack of emotion, social withdrawal), and cognitive impairment. Previously, we reported that the ethanolic extract of Prunella vulgaris var. lilacina attenuated the MK-801-induced schizophrenia-like behaviors such as prepulse inhibition (PPI) deficits and cognitive impairment in mice. The aim of the present study was to investigate whether danshensu isolated from P. vulgaris var. lilacina attenuates MK-801-induced sensorimotor gating dysfunction (PPI deficits), hyperlocomotion, and memory impairment in mice. Acute administration of danshensu (1, 3, or 10 mg/kg) significantly ameliorated the MK-801-induced PPI deficits in the acoustic startle response test. We also observed that the impaired recognition memory induced by MK-801 was attenuated by danshensu (1 mg/kg) in the novel object recognition test. However, danshensu failed to reverse the MK-801-induced hyperlocomotion in the open-field test. Collectively, the present results indicate danshensu would be an active agent for treating neuropsychiatric disorders such as schizophrenia.

• Progress in Medical Physics
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• v.25 no.3
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• pp.157-166
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• 2014

ATP in quantity co-stored with neurotransmitters in the secretory vesicles of neurons, by being co-released with the neurotransmitters, takes an important role to modulate the stimulus-secretion response of neurotransmitters. Here, in this study, the modulatory effect of ATP was studied in $Ca^{2+}$ channels of cultured rat adrenal chromaffin cells to investigate the physiological role of ATP in neurons. The $Ca^{2+}$ channel current was recorded in a whole-cell patch clamp configuration, which was modulated by ATP. In 10 mM $Ba^{2+}$ bath solution, ATP treatment (0.1 mM) decreased the $Ba^{2+}$ current by an average of $36{\pm}6%$ (n=8), showing a dose-dependency within the range of $10^{-4}{\sim}10^{-1}mM$. The current was recovered by ATP washout, demonstrating its reversible pattern. This current blockade effect of ATP was disinhibited by a large prepulse up to +80 mV, since the $Ba^{2+}$ current increment was larger when treated with ATP ($37{\pm}5%$, n=11) compared to the control ($25{\pm}3%$, n=12, without ATP). The $Ba^{2+}$ current was recorded with $GTP{\gamma}S$, the non-hydrolyzable GTP analogue, to determine if the blocking effect of ATP was mediated by G-protein. The $Ba^{2+}$ current decreased down to 45% of control with $GTP{\gamma}S$. With a large prepulse (+80 mV), the current increment was $34{\pm}4%$ (n=19), which $25{\pm}3%$ (n=12) under control condition (without $GTP{\gamma}S$). The $Ba^{2+}$ current waveform was well fitted to a single-exponential curve for the control, while a double-exponential curve best fitted the current signal with ATP or $GTP{\gamma}S$. In other words, a slow activation component appeared with ATP or $GTP{\gamma}S$, which suggested that both ATP and $GTP{\gamma}S$ caused slower activation of $Ca^{2+}$ channels via the same mechanism. The results suggest that ATP may block the $Ca^{2+}$ channels by G-protein and this $Ca^{2+}$ channel blocking effect of ATP is important in autocrine (or paracrine) inhibition of adrenaline secretion in chromaffin cell.

• Korean Journal of Biological Psychiatry
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• v.6 no.2
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• pp.153-160
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• 1999

Animal models can provide a useful tool for the study of some aspects of psychiatric disorders and their treatment. The four criteria for the evaluation of animal models of psychiatric disorders are as following : 1) similarity of inducing conditions 2) similarity of behavioral state 3) common underlying neurobiological mechanisms 4) reversal by clinically effective treatment techniques. Several animal models have been proposed for schizophrenia : phenylethylamine model, L-dopa model, hallucinogen model, cocaine model, amphetamine model, phencyclidine model, noradrenergic reward system lesion model, reticular stimulation model, social isolation model, conditioned avoidance reaction, catalepsy test, paw test, self-stimulation paradigms, latent inhibition paradigms, blocking paradigms, prepulse inhibition of the startle reflex, rodent interaction, social behavior in monkeys, hippocampal damage, high ambient pressure, and models using selective breeding. Among them, animals with bilateral lesion of the hippocampus may provide an adequate animal model for several symptoms of schizophrenia, and ketamine model can reproduce negative symptoms and cognitive deficits as well as positive symptoms of schizophrenia. In conclusion, no model of schizophrenia is entirely representative of the disease, and findings gleaned from model systems must be cautiously interpreted. Furthermore, the process of developing and validating animal models must work in concert with the process to identify reliable measures of human phenomenology.

• International Journal of Oral Biology
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• v.30 no.2
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• pp.71-76
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• 2005

The mesencephalic trigeminal nucleus (Mes V) contains cell bodies of primary afferent sensory neurons that relay proprioceptive information from the periodontium and masticatory muscles and function as typical sensory neurons or potentially as integrative interneurons. In the present study, we studied these two potential functions using combined experimental approaches of retrograde labeling and whole cell patch clamp recording. Mes V neurons that presumably originate from periodontal nerve fibers in subsets of Mes V nucleus were identified by retrograde labeling with a fluorescent dye, DiI, which was applied onto inferior alveolar nerve. These cells were elliptical perikarya shaped cells about $40{\mu}m$ in diameter. In these neurons, we measured high voltage-activated calcium channel (HVACC) currents. $GABA_B$ agonist, baclofen, inhibited calcium currents, and the HVACC currents inhibition by baclofen was voltage-dependent, exhibited prepulse facilitation, indicating that it was mediated by $G_i/_G_o$ protein. Taken together, our results demonstrate that Mes V neurons not only have cell bodies originating from periodontium, but also receive synaptic inputs including GABAergic neurons suggesting that Mes V neurons function as both primary sensory neurons and integrative interneurons.

• International Journal of Oral Biology
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• v.33 no.4
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• pp.143-147
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• 2008

The sodium bicarbonate cotransporter (NBC) protein is functionally expressed in salivary glands. In this experiment, we examined the role of NBC in $HCO_3^-$ formation in human parotid gland acinar cells. Intracellular pH (pHi) was measured in 2'-7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF)-loaded cells. Acetazolamide (0.1 mM) and 4,4'-diisothio cyanatostilbene-2,2'-disulphonic acid (DIDS, 0.5 mM) were used as specific inhibitors of carbonic anhydrase and NBC, respectively. The degree of inhibition was assessed by measuring the pHi recovery rate (${\Delta}pHi$/min) after cell acidification using an ammonium prepulse technique. In control experiments, ${\Delta}pHi$/min was $1.40{\pm}0.06$. Treatment of cells with 0.5 mM DIDS or 0.1 mM acetazolamide significantly reduced ${\Delta}pHi$/min to $1.14{\pm}0.14$ and $0.74{\pm}0.15$, respectively. Simultaneous application of DIDS and acetazolamide further reduced ${\Delta}pHi$/min to $0.47{\pm}0.10$. Therefore, DIDS and acetazolamide reduced ${\Delta}pHi$/min by 19% and 47%, respectively, while simultaneous application of both DIDS and acetazolamide caused a reduction in ${\Delta}pHi$/min of 67%. These results suggest that in addition to carbonic anhydrase, NBC also partially contributes to $HCO_3^-$ formation in human parotid gland acinar cells.

• Korean Journal of Medicinal Crop Science
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• v.24 no.5
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• pp.341-350
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• 2016

Background: Prenatal exposure to infectious and/or inflammatory insults can increase the risk of developing neuropsychiatric disorder such as bipolar disorder, autism, and schizophrenia later in life. We investigated whether Valeriana fauriei (VF) treatment alleviates prepulse inhibition (PPI) deficits and social interaction impairment induced by maternal immune activation (MIA). Methods and Results: Pregnant mice were exposed to polyriboinosinic-polyribocytidilic acid (5 mg/kg, viral infection mimic) on gestational day 9. The adolescent offspring received daily oral treatment with VF (100 mg/kg) and injections of clozapine (5 mg/kg) for 30 days starting on the postnatal day 35. The effects of VF extract treatment on behavioral activity impairment and protein expression were investigated using the PPI analysis, forced swim test (FST), open field test (OFT), social interaction test (SIT), and immunohistochemistry. The MIA-induced offspring showed deficits in the PPI, FST, OFT, and SIT compared to their non MIA-induced counterparts. Treatment with the VF extract significantly recovered the sensorimotor gating deficits and partially recovered the aggressive behavior observed in the SIT. The VF extract also reversed the downregulation of protein expression induced by MIA in the medial prefrontal cortex. Conclusions: Our results provide initial evidence of the fact that the VF extract could reverse MIA-induced behavioral impairment and prevent neurodevelopmental disorders such as schizophrenia.

• Korean Journal of Biological Psychiatry
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• v.21 no.4
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• pp.168-174
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• 2014

Objectives Sensory gating dysfunctions in patients with schizophrenia and bipolar disorder have been investigated through two similar methods ; P50 suppression and prepulse inhibition paradigms. However, recent studies have demonstrated that the two measures are not correlated but rather constitute as distinct neural processes. Recent studies adopting spectral frequency analysis suggest that P50 suppression reflects the interaction between gamma and other frequency bands. The aim of the present study is to investigate which frequency component shows more significant interaction with gamma band. Methods A total of 108 mood disorder patients and 36 normal subjects were included in the study. The P50 responses to conditioning and test stimuli with an intra-pair interval of 500 msec were measured in the study population. According to P50 ratio (amplitude to the test stimulus/amplitude to the conditioning stimulus), the subjects with P50 ratio less than 0.2 were defined as suppressed group (SG) ; non-suppressed group (NSG) consisted of P50 ratio more than 0.8. Thirty-five and 25 subjects were included in SG and NSG, respectively. Point-to-point correlation coefficients (PPCCs) of both groups were calculated between two time-windows : the first window (S1) was defined as the time-window of one hundred millisecond after the conditioning auditory stimulus and the second window (S2) was defined as the time-window of 100 msec after the test auditory stimulus. Spectral frequency analysis was performed to investigate which frequency band results in the difference of PPCC between SG and NSG. Results Significant reduction of PPCC between S1 and S2 was observed in the SG (Pearson's r = 0.24), compared to PPCC of the NSG (r = 0.58, p < 0.05). In spectral frequency analysis, gamma band showed "phase-reset" and similar responses after the two auditory stimuli in suppressed and non-suppressed group. However in the case of alpha band, comparison showed significantly low PPCC in SG (r = -0.14) compared to NSG (r = 0.36, p < 0.05). This may be reflecting "phase-out" of alpha band against gamma band at approximately 50 msecs after the test stimulus in the SG. Conclusions Our study suggests that normal P50 suppression is caused by phase-out of alpha band against gamma band after the second auditory stimulus. Thus it is demonstrated that normal sensory gating process is constituted with attenuated alpha power, superimposed on consistent gamma response. Implications of preserved gamma and decreased alpha band in sensory gating function are discussed.