S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Medicine (의학과) Theses (Ph.D. / Sc.D._의학과)
The Difference of Sound-specific Response in Rat Auditory Cortical Activation Pattern between Normal Hearing and Unilateral Deaf: Multi-Channel Neural Recording Study
정상 청력과 일측성 난청에서 자극음에 따른 쥐 청각 피질 활성의 특이 반응의 차이: 다채널 신경 기록 연구
- 의과대학 의학과
- Issue Date
- 서울대학교 대학원
- 학위논문 (박사)-- 서울대학교 대학원 : 의학과, 2017. 2. 오승하.
- Introduction: The reorganization of auditory cortex is achieved through sound-dependent plasticity and has a brief postnatal period of heightened nervous system receptivity which is commonly referred to as the critical period. The aims of this study are to assess the differences of sound-specific neural responses in rat auditory cortical activation patterns in the normal hearing rats and unilateral deafening rats of young and adult periods.
Material and methods: Experiments were performed on the 81 Sprague–Dawley rats
normal hearing (NH) group: 45 rats, young single-sided deafness (YSSD) group: 17 rats and adult single-sided deafness (ASSD) group: 19 rats. To evaluate normal auditory cortex development in the NH group, we recorded multi-unit neural activities at the age of P2w, P2w4ds, P3w4ds, P4w4ds, P5w4ds, P6w4ds, P7w4ds, P8w4ds, P9w4ds and P10w4ds. In the YSSD group, left side cochlear ablations were done at the age of P10ds and multi-neural recordings were implemented at the post-deafening (PD) 2w, PD4w, PD6w and PD8w. In the ASSD group, left side cochlear ablations were done at the age of P53ds and multi-neural recording were conducted at the PD2w, PD4w, PD6w and PD8w. The both hearing thresholds were < 40 dB sound pressure level (SPL) for NH group and the left side hearing thresholds > 80 dB SPL and the right side hearing threshold < 40 dB SPL for SSD groups. A craniotomy was made over both temporal cortices spanning from Bregma to Lambda, and the auditory cortex surface area was presumed based on the vascular pattern and anatomic position. After fixation of the animal in the stereotaxic frame, a tungsten wire-based 16 channel microelectrode array (4x4 array, diameter: 35 μm, inter-electrode spacing 600 μm, 45° angled tip, impedance 300 k at 1 kHz in phosphate-buffered saline) was inserted perpendicular to the surface of the auditory cortex to a depth of 600 ~ 900 μm for layer IV of auditory cortex. Gaussian white sound stimulation (80 dB SPL, 100 ms duration) was generated and introduced to the right ear every 500 ms. The classification of multi-units per electrode was done with multichannel acquisition processor. One unit which had the greatest peak amplitude was chosen and the Peri-stimulus time histogram (PSTH) was optimized (observation period: 500 ms, time bin width: 3 ms, number of trials: 200). The significant neural response was named ‘responsive’ when the peak amplitude of PSTH was over 10 spikes/bin and synchronized with the sound stimulus. The parameters were onset latency, peak latency, peak amplitude, contralaterality index and total responsive area. To visualize and calculate the total responsive area to the sound stimulus, auditory cortex map was reconstructed using Voronoi tessellation method. The total responsive area for each hemisphere was calculated using Image J statistical analyses. The Data were analyzed with SPSS software for Windows version 21.0 (IBM SPSS statistics, Armonk, NY, USA). The criterion for statistical significance was set at p < 0.05.
Results: In the NH group, we found a larger peak amplitude and total responsive area and a shorter peak latency of the contralateral hemisphere and the contralateral preference to sound stimulation was observed in the all ages. After the unilateral deafening (left ear), the larger contralateral peak amplitude of normal hearing was maintained in the YSSD group but disappeared in the ASSD in which the peak amplitudes of both hemispheres showed gradually similar responses until post-deafening of 8 weeks. The shorter contralateral peak latencies of NH group disappeared in the YSSD group at the 2 weeks after deafening but recovered from post-deafening 4 weeks to 8 weeks. Whereas in the ASSD group, the shorter contralateral peak latencies maintained until 6 weeks after deafening and then both hemisphere had the almost similar peak latencies. The larger contralateral total reactive responsive area of NH group disappeared and showed reversed responses in the YSSD group from 2 weeks through 4 weeks after unilateral deafening, and then came to recover contralateral larger area from post-deafening of 6 weeks through 8 weeks. Whereas in the ASSD group contralateral responsive area was abruptly decreased at the 4 weeks after unilateral deafening and had gradual increases with ipsilateral responsive area until post-deafening of 8 weeks, and then both hemispheres came to have similar total reactive areas.
Conclusion: After unilateral deafening, typical contralateral dominance of hearing ear was no longer evident, and different response characteristics were seen according to the deaf onset time and period of deafening. The YSSD group’s sensitive period of reorganization after deafening was about 4 weeks from just after deafening but that of ASSD group was only 2 weeks from post-deafening of 4 weeks. This result suggests that there is specific timing involved in rehabilitation of young and adult unilateral hearing loss.