Hidekazu Furuse

Reliability of 80-Hz Amplitude- Modulation-Following Response Detected by Phase Coherence

The reliability and frequency specificity of the 80-Hz amplitude-modulation-following response (80-Hz AMFR) during sleep detected by phase coherence as a measure of the hearing threshold was evaluated in 169 affected ears of 125 children with hearing impairment. The 80-Hz AMFR at a carrier frequency of 1000 Hz was monitored in all 169 ears and the auditory brainstem response (ABR) elicited by 1000-Hz tone pips was evaluated in 93 ears. Both responses were examined during sleep, and the thresholds were compared with the behavioral hearing threshold, which was determined by standard pure-tone audiometry or play audiometry. In 24 ears of 22 children with various patterns of audiogram, the 80-Hz AMFR was examined at different carrier frequencies, and the threshold pattern was compared with the pure-tone audiogram to investigate the frequency specificity of 80-Hz AMFR. The mean and standard deviation of the difference between the 80-Hz AMFR at a carrier frequency of 1000 Hz and pure-tone thresholds of 1000 Hz was 3.8 and 12.9 dB, and that between the ABR and pure-tone thresholds was 6.8 and 14.1 dB, respectively. The threshold patterns of 80-Hz AMFR clearly followed the corresponding audiogram patterns in all types of hearing impairment. The measurement of 80-Hz AMFR thus appears to be accurate in hearing assessment and to have good frequency specificity in children during sleep.

Pure-tone threshold prediction by 80-Hz amplitude-modulation following response.

The usefulness of 80-Hz amplitude-modulation following response (AMFR) detected by phase spectral analysis to predict the hearing threshold during sleep was evaluated in 20 normal adults, 8 normal children and 37 children with hearing impairment. The onset effect of tonal stimulus on 80-Hz steady state response was studied in normal adults during sleep and a threshold of 80-Hz AMFR detected by phase spectral analysis was compared with that of ABR elicited by tone pips in children during sleep. Although 80-Hz AMFR is not appropriate for the assessment of hearing in adults, it appears useful for evaluating hearing in young children during sleep. Hearing prediction by 80-Hz AMFR appears to be more accurate than that by ABR elicited with tone pips. The onset effect of stimulus on 80-Hz AMFR with modulation depth of 95% was less than 80-Hz SSR evoked by clicks.

The mechanism of ATP-induced long-term potentiation involves extracellular phosphorylation of membrane proteins in guinea-pig hippocampal CA1 neurons ☆

The mechanism of ATP-induced long-term potentiation was studied pharmacologically using guinea-pig hippocampal slices. Application of 1-10 microM ATP for 10 min transiently depressed and then slowly augmented the synaptic transmission in CA1 neurons leading to long-term potentiation (LTP). This ATP-induced LTP was blocked by the addition of K-252b, an ecto-protein kinase inhibitor, but was enhanced by the addition of RK682, an ecto-phosphatase inhibitor, both of which do not permeate the cell membrane. These results suggest that ATP applied to the perfusate provides enough substrate for ecto-protein kinase to induce LTP through phosphorylation of extracellular domains of membrane proteins in CA1 neurons.

Effect of the mono- and tetra-sialogangliosides, GM1 and GQ1b, on long-term potentiation in the CA1 hippocampal neurons of the guinea pig

Abstract Effects of the mono- and tetra-sialogangliosides, GM1 and GQ1b, on long-term potentiation (LTP) were investigated in the CA1 neurons of guinea-pig hippocampal slices. The magnitude of LTP induced by a strong tetanus (100 Hz, 100 pulses) was not significantly affected by application of either ganglioside. In contrast, when LTP was induced by a weak tetanus (100 Hz, 4 pulses), a significantly greater LTP was induced in the presence of either ganglioside. Similarly, when slices were incubated in low-Ca2+ (1.0–1.1 mM) medium for more than 2 h, the LTP was usually small or absent, but showed a significant increase in amplitude of population spike (A-PS) when the slices were incubated with either GM1 or GQ1b (4–5 µg/ml). In addition, the application of GQ1b (4 µg/ml) reversed the blocking effect of an NMDA-receptor antagonist, APP-5 (10 µM), on the induction of LTP and resulted in forming LTP. Based on these findings, we conclude that GM1 and GQ1b exert positive modulatory effects on the induction of LTP in hippocampal CA1 neurons and suggest that GM1 and GQ1b may participate in the induction of LTP as donors of Ca2+ ions.

Voltage-gated Ca2+ channel blockers, ω-AgalVA and Ni2+, suppress the induction of θ-burst induced long-term potentiation in guinea-pig hippocampal CA1 neurons

Abstract It is widely believed that a rise in post-synaptic calcium concentration ([Ca 2+ ];) is a necessary step in the induction of long-term potentiation (LTP) (Bliss and Collingridge, Nature, 361 (1993) 31–39). In this experiment, we examine the involvement of voltagegated Ca 2+ channels (VGCC) in the induction of AP5-sensitive LTP induced by θ-burst stimulation in guinea-pig hippocampal CA1 neurons. The VGCC blockers, Ni 2+ , (25 μM, T -channel blocker) or ω-AgaIVA (60 nM, P-channel blocker), which have no effect on synaptic transmission, suppress 60% or 78% of the Θ-burst induced UP, respectively. This implies that Ca 2+ entry through VGCC is an important step in this form of LTP.

The long-term suppressive effect of prior activation of synaptic inputs by low-frequency stimulation on induction of long-term potentiation in CA1 neurons of guinea pig hippocampal slices

We have investigated the effects of prior activation of afferent inputs by a train of low-frequency stimulation (LFS) on the induction of long term potentiation (LTP) induced by highfrequency stimulation (tetanus, 100 Hz, 100 pulses) in CA1 neurons of guinea pig hippocampal slices. The parameters of the LFS were altered systematically: the frequency (1 or 5 Hz); the number of pulses (80, 200 or 1000); and the time lag from the LFS to the tetanus (20, 60 or 100 min). Conditioning effects of the LFS on the induction of LTP were evaluated in terms of the slope of the field excitatory postsynaptic potential (S-EPSP) and the amplitude of the population spike (A-PS). LTP could reliably be induced by 100 Hz tetanic stimulation delivered to a naive slice. In contrast, the attempt to induce LTP 60 min after LFS of 200 or 1000 pulses at 1 Hz resulted only in short-term potentiation while the LFS itself produced no significant change in the responses. The suppressive effect on LTP was significantly reduced for 1 Hz LFS with a smaller number of pulses (80 pulses), or a shorter (20 min) or longer (100 min) time lag from the LFS to the tetanus, or with LFS at a higher frequency (5 Hz). When the LFS of 1000 pulses at 1 Hz was delivered in the presence of the n-methyl-d-aspartate (NMDA) receptor antagonist AP5 (d,l-4-amino-5-phosphonovalerate, 50 μM), which was washed out after the end of the LFS, the tetanus given 60 min after application of the LFS produced stable LTP, indicating the involvement of NMDA receptor/channels in the mechanisms of this particular form of synaptic plasticity-long-term suppression of LTP.We have investigated the effects of prior activation of afferent inputs by a train of low-frequency stimulation (LFS) on the induction of long term potentiation (LTP) induced by highfrequency stimulation (tetanus, 100 Hz, 100 pulses) in CA1 neurons of guinea pig hippocampal slices. The parameters of the LFS were altered systematically: the frequency (1 or 5 Hz); the number of pulses (80, 200 or 1000); and the time lag from the LFS to the tetanus (20, 60 or 100 min). Conditioning effects of the LFS on the induction of LTP were evaluated in terms of the slope of the field excitatory postsynaptic potential (S-EPSP) and the amplitude of the population spike (A-PS). LTP could reliably be induced by 100 Hz tetanic stimulation delivered to a naive slice. In contrast, the attempt to induce LTP 60 min after LFS of 200 or 1000 pulses at 1 Hz resulted only in short-term potentiation while the LFS itself produced no significant change in the responses. The suppressive effect on LTP was significantly reduced for 1 Hz LFS with a smaller number of pulses (80 pulses), or a shorter (20 min) or longer (100 min) time lag from the LFS to the tetanus, or with LFS at a higher frequency (5 Hz). When the LFS of 1000 pulses at 1 Hz was delivered in the presence of the n-methyl-d-aspartate (NMDA) receptor antagonist AP5 (d,l-4-amino-5-phosphonovalerate, 50 μM), which was washed out after the end of the LFS, the tetanus given 60 min after application of the LFS produced stable LTP, indicating the involvement of NMDA receptor/channels in the mechanisms of this particular form of synaptic plasticity-long-term suppression of LTP.

Effects of Aging on Amplitude-modulation Following Response

Phase spectral analysis as developed by Fridman (1982) was used to detect amplitude-modulation following response (AMFR). The threshold of AMFR was determined with greater sensitivity and accuracy by phase spectral analysis than by visual analysis. Using this method, a modulation frequency (MF) of 80 Hz was found optimal for detecting AMFR in young children (ranging in age from 2 to 4 years) during sleep, for whom there is no advantage in recording 40-Hz steady-state responses. To determine the optimal MF for detecting AMFR during sleep in children less than 2 years of age and age limitation for using 80-Hz MAFR in objective audiometry, AMFR as a function of MF was investigated during sleep in 25 children with normal hearing ranging from 4 months to 15 years of age, and 10 normal hearing adults. The stimulus was a 1000 Hz, 50 dBnHL sinusoidally amplitude modulated tone with a modulation depth of 95%. MF was varied from 20 to 200 Hz in 20 Hz steps. Response was determined by phase spectral analysis and the S/N ratio calculated by spectral amplitude at the modulation frequency and noise level around the modulation frequency using fast Fourier transform. Phase spectral analysis showed AMFR at MF of 80 Hz to be the most stable and reliable in all children during sleep among MFs from 20 to 200 Hz. Spectral amplitude analysis demonstrated 80-Hz AMFR to have a high S/N ratio in all children.(ABSTRACT TRUNCATED AT 250 WORDS)

Detectability of Amplitude-modulation Following Response at Different Carrier Frequencies

To assess the detectability of amplitude-modulation following response (AMFR) elicited at different carrier (CFs) and modulation frequencies (MFs) during sleep, as well as the usefulness of AMFR in evoked response audiometry, AMFR was examined in 10 adults with normal hearing while sleeping. The stimulus was a 50 dBnHL sinusoidally amplitude-modulated (SAM) tone with a modulation depth of 95%. The MF of the stimulus tone was varied from 20 to 120 Hz in 20 Hz steps and CFs were 500, 1000, 2000 and 4000 Hz. An SAM tone with a CF of 20,000 Hz was used for stimulation in 5 subjects to confirm that the response did not contain any artifact. Response was determined by phase spectral analysis. The component synchrony measure of AMFRs at MF of 40 Hz (40-Hz AMFR) was high at lower CFs, but 40-Hz AMFRs at higher CFs were unreliable. The detectability of 80-Hz AMFR was high for all CFs. It was confirmed that the response waveform was not contaminated by any electromagnetic artifact. Eighty-Hz AMFR detected by phase spectral analysis should thus be useful for predicting frequency-specific hearing thresholds during sleep.