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論文名稱(外文):Acoustic reflexes: potential use in probing tinnitus in animal models
指導教授(外文):Wai-Fung Poon
外文關鍵詞:tinnitushead orientingpinna reflexvibrissa freezing response
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評估耳鳴在動物中表現與否,最常使用的方法其一為利用學習行為的條件反射(polydipsia avoidance);另一方法為觀察前脈衝抑制作用 (pre-pulse inhibition)對於抑制聽覺驚嚇反射的有無。此兩種方法皆有其利弊:條件反射對於耳鳴表現的測量儘管較為準確,但它需要花費長時間的訓練;利用聽覺驚嚇反射不需進行行為訓練,但是其須利用高強度的聲音刺激(大於90分貝),相較於耳鳴所感知的聲音(小於35分貝)高出許多。因此,若能利用其他可在低強度聲音下引發的聽覺反射來測量耳鳴將非常有幫助。然而這些反射的特性,尤其在接近耳鳴強度的聲音刺激下,還尚未被報告(頭部轉向反射、耳廓反射、恐懼凍結反射)。為了研究這些反射,我們開發了一種影像記錄系統。並且使用一系列聲音訊號(包括預先錄製廣頻的自然聲音)將實驗中動物發生適應的情形降到最低。在成年大白鼠中,我們觀察到(1)頭部轉向反射之反應潛伏期通常較長(大約150毫秒);(2)同時發生的單側耳廓反射潛伏期則較短(大約50毫秒);(3)觸鬚的恐懼凍結反射亦具有較短反應潛伏期(大約80毫秒)。不同的反應潛伏期暗示這三種反射所牽涉的神經路徑並不完全相同。最重要的,這三種反射都可以在聲音強度低於40分貝時引發。在早期聲音刺激所引發的耳鳴動物模式中,初步結果顯示大白鼠聽覺閾值有上升的趨勢,可能來自耳鳴或是聽覺損壞引起之遮蔽作用。此結果強烈暗示這些聽覺反射可以做為一個簡單且客觀的工具,探測耳鳴的發生與否。
In estimating the presence of tinnitus in animals, a conditioned behavior (polydipsia avoidance) and a reflexive behavior (pre-pulse inhibition acoustic startle reflex) are commonly used. Both of them have strength and weakness: polydipsia avoidance is more accurate, but requires long period of training; acoustic startle reflex requires no training but it only occurs at high sound intensity levels (〉90 dB SPL), way above that of tinnitus percept (〈 35 dB SPL). Hence, the use of other kinds of acoustic reflexes that can be elicited at low intensities would be very beneficial. However, the characterization of other acoustic reflexes (head orienting reflex, pinna reflex, freezing reflex) has not been done especially at low intensity levels where tinnitus is typically perceived. Here an imaging system is developed to study three acoustic reflexes. To minimize habituation, a host of acoustic signals are presented (including a set of pre-recorded environmental sounds with broad spectra). In the control adult rats: (a) head orienting reflex was often observed at a longer latency (~150 ms); (b) concurrent with this, pinna movements that are ipsi-lateral to sound source with response latency ~50 ms; (c) vibrissa freezing response that appeared with much shorter latency (~80 ms). The different response latencies are consistent with the different central neural pathways underlying these reflexes. Most importantly, all of these reflexes could be induced by sounds at levels below 40 dB SPL. Preliminary study on a putative tinnitus animal model (early sound exposure) indicated a trend of threshold elevation suggesting the presence of masking likely due to tinnitus or hearing loss. Results strongly suggested that these acoustic reflexes could be potentially useful as a simple and objective means of probing the tinnitus.
Abstract I
Chinese Abstract III
Acknowledgment IV
Contents V
List of figures VIII

1. Introduction 1
1.1 Tinnitus 1
1.2 Ototoxic drugs and tinnitus 3
1.3 Sound exposure and tinnitus 4
1.4 Behavioral assessment of experimental tinnitus 5
1.4.1 Conditional reflex – polydipsia avoidance 5
1.4.2 Acoustic startle reflex - silence gap detection in tinnitus 6
1.5 Potential use of other acoustic reflexes in probing tinnitus 7
1.6 Previous methods to study pinna movement 8
1.7 Aims of study 10
2. Materials and Methods 11
2.1 Animal 11
2.2 Image recording 11
2.3 Experimental paradigm 12
2.4 Sound exposure paradigm 12
2.5 Acoustic stimulation for eliciting acoustic reflexes 13
2.6 Video recording 13
2.7 Data analyses 14
2.7.1 Determination of the pre-stimulus location of rats 15
2.7.2 Movement descriptors 15 Standardization of movement parameters 15 Analysis of the head orienting response 16 Analysis of the acoustic pinna reflex 17 Analysis of the vibrissa freezing response 18
3. Results 20
3.1 Animal location in the behavioral test box 20
3.1.1 Distribution of head position 21
3.1.2 Distribution of head orientation 21
3.2 Behavioral response to complex sound 21
3.2.1 Characteristics of the head orienting response 21
3.2.2 Characteristics of the pinna reflex 22
3.2.3 Characteristics of the vibrissa freezing response 24
3.2.4 Trials with mixed responses 25
3.2.5 Comparison among head orienting, pinna reflex and vibrissa freezing responses 25
3.2.6 Comparison of responses between the control and sound-exposed groups 26
4. Discussion 27
4.1 Characteristics of the pinna reflex, head orienting and vibrissa freezing responses 27
4.2 Responses in the sound-exposed group 29
4.3 Future improvement in methodology 30
5. Conclusion 31
6. References 33
7. Figures 42
8. Appendices 91

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