大鼠单侧耳蜗损毁对听中枢不同部位r-氨基丁酸能神经元分布的影响
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摘要
目的：探讨正常大鼠畸变产物耳声发射(DPOAE)的基本特征，为动物的筛选及动物模型建立的评估提供参考资料。研究大鼠单侧耳蜗损毁前后不同部位、不同时期，耳蜗核、下丘及听皮层中GABA能阳性神经元的分布及数量。
方法：采用CELESTA-503型耳声发射分析仪对40只(80耳)健康大鼠行DPOAE“听力图”和输入／输出曲线及阈值测试。按Catherine法对实验动物行单侧耳蜗毁损，标本行石蜡包埋、切片，并应用免疫组化方法(SP法)行耳蜗核、下丘及听皮层中GABA能阳性神经元分布的检测。
结果：1) 各频率的DPOAE检出率均为100％；1kHz的DPOAE幅值为17.60±5.96dBSPL，反应阈值为36.67±3.83dBSPL；2kHz以上DPOAE幅值均大于25dBSPL，反应阈值低于1kHz；I／O曲线表明各频率DPOAE幅值随初始音的强度上升而增加，两者间存在极为显著的相关性；同频率、同强度，DPOAE幅值、反应阈值，两耳间差异均无显著性(P＞0.05)。单侧耳蜗毁损后大鼠手术侧DPOAE幅值未引出。2) GABA能阳性神经元广泛分布于听觉中枢，听皮层中数量最多，耳蜗核次之，下丘中最少。GABA能神经元的体积，以下丘中最大、着色较深，听皮层次之、着色也较深，耳蜗核中最小、着色很深。耳蜗核中GABA能阳性神经元的数目：术后1至2周手术同侧明显低于对侧，术后3周上升，但仍少于手术对侧，至术后1月，手术同侧略少于对侧，且差异无显著性(P＞0.05)。下丘中GABA阳性神经元的数目：术后1至3周手术对侧明显低于同侧，至术后1月，手术对侧GABA阳性神经元的数目增加，但仍少于手术侧，且有显著性差异(P＜0.05)。听皮层中GABA阳性神经元的数目：术后1至2周手术对侧明显低于手术侧，术后3周上升，但仍少于手术侧，至术后1月，手术对侧略少于手术侧，且差异无显著性(P＞0.05)。
结论：1) 大鼠的DPOAE检出率高，幅值大，各项指标反应稳定。单侧耳蜗毁损动物可作为本研究的动物模型。2) 单侧耳蜗损毁前后，GABA能阳性神经元的分布在耳蜗核、下丘及听皮层中呈一明显的动态变化过程，说明GABA能神经元参与了耳蜗毁损后听觉中枢的可塑性变化或功能重组的过程，提示GABA能神经元数目的增减可能为听觉中枢的重组所必需。
Object: To explore the basic properties of distortion product otoacoustic emission (DPOAE) in normal rats and to observe the distribution of gama-aminobutyric acid (GABA) ergic neurons in rat auditory center in pre and post-operation.
Methods: DP-gram, I/O function curves and threshold of forty rats were measured by CELESTA-503 Cochlear Emission Analyzer. The technique of direct anti-GABA imrnunocytochemistry (SP) was used in this study.
Results: 1) The incidence of DPOAE in all frequencies were 100%.The amplitude of DPOAE in 1kHz was 17.60?.96dBSPL. The amplitudes of DPOAE above 2kHz were larger than 25dBSPL. I/O function curves demonstrated that there was a significant relation betweem the amplitudes of DPOAE and the levels of primary stimuli in the statistics, that is, the higher levels of primary stimuli was, the larger amplitudes of DPOAE was. There was not a significant difference between left ears and right ears in all indeies. We could not obtain the amplitudes of DPOAE in lesion side of unilateral cochlea ablation rats. 2) The GABAergic neurons existed extensively in auditory center:auditory cortex(AC), inferior colliculus(IC) and cochlear nuclei(CN). But the number ,shape and staining of GABAergic neurons were different in every nucleus. AC had the largest number of GABAergic neuron, CN was second, IC had less GABAergic cells.The volume of GABAergic cells in IC was larger than those in AC and CN, and stained heavy. The GABA cells
in CN was more heavily staining than those in IC and AC.In CN, the number of GABAergic cells in lesion side was less than those in intact side after unilateral cochlea ablation one to two weeks, then the number of GABAergic cells increased after three weeks and almost reached normal number in a month of post-operation,the difference has no statistically significance(P>0.05). In IC,the number of GABAergic cells in intact side was less than those in lesion side after unilateral cochlea ablation one to three weeks, then the number of GABAergic cells increased but stiil less than that of normal number in a month of post-operation,which showed significant difference between intact and lesion sides(P<0.05). In AC, the number of GABAergic cells in intact side was less than those in lesion side after unilateral cochlea ablation one to two weeks,then the number of GABAergic cells increased after three weeks and almost reached normal number in a month of post-operation(P>0.05).
Conclusion: 1) In rats, the incidence of DPOAE was high, the amplitudes of
DPOAE was larger and all indeies were stabilization.The rat of unilateral cochlea ablation could serve for father study.2) The changes of GABAergic neurons reflect the balance between excitatory and inhibitory of neurons, it suggest that changes in the extent of GABAergic inhibition have been shown to contribute to the reorganization of auditory central system after unilateral cochlea ablation in rats.
方法：采用CELESTA-503型耳声发射分析仪对40只(80耳)健康大鼠行DPOAE“听力图”和输入／输出曲线及阈值测试。按Catherine法对实验动物行单侧耳蜗毁损，标本行石蜡包埋、切片，并应用免疫组化方法(SP法)行耳蜗核、下丘及听皮层中GABA能阳性神经元分布的检测。
结果：1) 各频率的DPOAE检出率均为100％；1kHz的DPOAE幅值为17.60±5.96dBSPL，反应阈值为36.67±3.83dBSPL；2kHz以上DPOAE幅值均大于25dBSPL，反应阈值低于1kHz；I／O曲线表明各频率DPOAE幅值随初始音的强度上升而增加，两者间存在极为显著的相关性；同频率、同强度，DPOAE幅值、反应阈值，两耳间差异均无显著性(P＞0.05)。单侧耳蜗毁损后大鼠手术侧DPOAE幅值未引出。2) GABA能阳性神经元广泛分布于听觉中枢，听皮层中数量最多，耳蜗核次之，下丘中最少。GABA能神经元的体积，以下丘中最大、着色较深，听皮层次之、着色也较深，耳蜗核中最小、着色很深。耳蜗核中GABA能阳性神经元的数目：术后1至2周手术同侧明显低于对侧，术后3周上升，但仍少于手术对侧，至术后1月，手术同侧略少于对侧，且差异无显著性(P＞0.05)。下丘中GABA阳性神经元的数目：术后1至3周手术对侧明显低于同侧，至术后1月，手术对侧GABA阳性神经元的数目增加，但仍少于手术侧，且有显著性差异(P＜0.05)。听皮层中GABA阳性神经元的数目：术后1至2周手术对侧明显低于手术侧，术后3周上升，但仍少于手术侧，至术后1月，手术对侧略少于手术侧，且差异无显著性(P＞0.05)。
结论：1) 大鼠的DPOAE检出率高，幅值大，各项指标反应稳定。单侧耳蜗毁损动物可作为本研究的动物模型。2) 单侧耳蜗损毁前后，GABA能阳性神经元的分布在耳蜗核、下丘及听皮层中呈一明显的动态变化过程，说明GABA能神经元参与了耳蜗毁损后听觉中枢的可塑性变化或功能重组的过程，提示GABA能神经元数目的增减可能为听觉中枢的重组所必需。
Object: To explore the basic properties of distortion product otoacoustic emission (DPOAE) in normal rats and to observe the distribution of gama-aminobutyric acid (GABA) ergic neurons in rat auditory center in pre and post-operation.
Methods: DP-gram, I/O function curves and threshold of forty rats were measured by CELESTA-503 Cochlear Emission Analyzer. The technique of direct anti-GABA imrnunocytochemistry (SP) was used in this study.
Results: 1) The incidence of DPOAE in all frequencies were 100%.The amplitude of DPOAE in 1kHz was 17.60?.96dBSPL. The amplitudes of DPOAE above 2kHz were larger than 25dBSPL. I/O function curves demonstrated that there was a significant relation betweem the amplitudes of DPOAE and the levels of primary stimuli in the statistics, that is, the higher levels of primary stimuli was, the larger amplitudes of DPOAE was. There was not a significant difference between left ears and right ears in all indeies. We could not obtain the amplitudes of DPOAE in lesion side of unilateral cochlea ablation rats. 2) The GABAergic neurons existed extensively in auditory center:auditory cortex(AC), inferior colliculus(IC) and cochlear nuclei(CN). But the number ,shape and staining of GABAergic neurons were different in every nucleus. AC had the largest number of GABAergic neuron, CN was second, IC had less GABAergic cells.The volume of GABAergic cells in IC was larger than those in AC and CN, and stained heavy. The GABA cells
in CN was more heavily staining than those in IC and AC.In CN, the number of GABAergic cells in lesion side was less than those in intact side after unilateral cochlea ablation one to two weeks, then the number of GABAergic cells increased after three weeks and almost reached normal number in a month of post-operation,the difference has no statistically significance(P>0.05). In IC,the number of GABAergic cells in intact side was less than those in lesion side after unilateral cochlea ablation one to three weeks, then the number of GABAergic cells increased but stiil less than that of normal number in a month of post-operation,which showed significant difference between intact and lesion sides(P<0.05). In AC, the number of GABAergic cells in intact side was less than those in lesion side after unilateral cochlea ablation one to two weeks,then the number of GABAergic cells increased after three weeks and almost reached normal number in a month of post-operation(P>0.05).
Conclusion: 1) In rats, the incidence of DPOAE was high, the amplitudes of
DPOAE was larger and all indeies were stabilization.The rat of unilateral cochlea ablation could serve for father study.2) The changes of GABAergic neurons reflect the balance between excitatory and inhibitory of neurons, it suggest that changes in the extent of GABAergic inhibition have been shown to contribute to the reorganization of auditory central system after unilateral cochlea ablation in rats.
引文
1. Harrison RV, Nagasawa A, Smith DW, et al. Reorganization of auditory cortex after neonatal high frequency cochlear heating loss. Hear Res, 1991,54:11-19
2. Robertson D and Irvine DRF. Plasticity of frequency organization in auditory cortex of guinea pigs partial unilateral deafess. J Comp Neurol, 1989,282:456-471
3. Willott JF and Lu S-M. Noise-induced heating loss can alter neural coding and increase excitability in the central nervous system. Science Wash, 1982,216:1331-1332
4. Han MH, Li Y, Yang XL. Desensitizing GABAc receptors on carp retinal bipolar cells. Neuro Report, 1997,8:1331-1335
5. Amin J, Weiss DS. homomeric 1 GABA channels:activation properties and domain. Receptor Channels, 1994,2:227-236
6. Pan ZH, Lipton SA. Multiple GABA receptor subtypes mediate inhibition of calcium influx at rat retinal bipolar cell terminals. J Neurosci, 1995,15:2668-2679
7. Barker JL, Behal T, Li Y-X, et al. GABAergic cells and signals in CNS development. Perspect Dev Neurobiol, 1998,5:305-322
8. Patricia V, Zoya K, Emilia M. GABAsignalling during development: new data and old question. Cell Tissue Res, 2001,305:239-246
9．周晓明，孙心德．单耳堵塞对蝙蝠下丘GABA阳性反应神经元的影响．[J]生物物理学报，1999，15(1)：218-224
10．杨卫平，武文明，方耀云等．老年大鼠耳蜗核r-氨基丁酸免疫反应的变化．中华医学杂志，1998，78(1)：30-32
11. Tamáis G, Buhl EH, Lorinc ZA, et al. Proximally targeted GABAergic synapses and gap junctions synchronize cortical interneurons. Natl Neurosci, 2000,3:366-371
12. Crook JM, Kisvarday ZF, Eyselut. Evidence for a contribution of lateral inhibition to orientation tuning and direction selectivity in cat visual cortex: reversible inactivation of functionally characterized sites combined with neuroanatomical tracing techniques. Eur J Neurosci, 1998,10:2056-2075
13. Kyriaxl HT, Carvell GE, Brumberg JC, et al. Quantitative effects of GABA and bicuculline methiodide on receptive field properties of neurons in real and simulated whisker barrels. J Neurophysiol, 1996,75:547-560
14. Wang J, Caspary DM, Salvi RJ. GABA-A antagonist causes dramatic expansion of
tuning in primary auditory cortex. Neuroreport, 2000,11:1137-1140
1. Kimberley BP, Brown DK, Eggermont JJ. Measuring human cochler travelling wave delay using distortion product emission phase responses. J Acoust Soc Am, 1993,94:1343
2. Martin GR, Ohlms LA, Franklin DJ, et al. Distortion product emission in human Ⅲ, influences of sensorineural loss. Ann Otol Rhinol Laryngol, 1990,99:30
3. Probst R, Lonsbury-martin BL, Martin G. A review of otoacoustic emissions. J Acoust Soc Am, 1991,89:2027
4．哈里逊著，赵月华主译．哈里逊内科学(下册)．神经系统疾病．北京人民卫生出版社，1994，2306-2433
5. S.K. Suneja, S.J. Potashner, C.G. Benson. Plastic changes in Glycine and GABA release and uptake in adult brainstem auditory nuclei after unilateral middle ear ossicle removal and cochlear ablation. Experimental neurology, 1998,151:273-288
6. Catherine DW, Gérard L, Antonio CT, et al. Lack of growth-associated protein-43 reemergence or of growth-associated protein-43 mRNA modulation in deafferented vestibular nuclei during the first 6 weeks after nuilateral inner ear lesion.Exp Brain Res, 2000,132:464-475
7. Smurzynski J, Kim DO. Distortion-product and click-evoked otoacoustic emission of normally hearing adults. Hear Res, 1992,58:227-240
8. Lonsbury-Martin BL, Martin GK. The clinical application of acoustic distortion products. Otolaryngol Head-Neck Surgery, 1990,103:52
9. Dallos P.The active cochlear. J Neuro Sci, 1992,12(2):4575-4585
10. Hauser R, Probest R. The influence of systematic primary-tone level variation L_1-L_2 on the acoustic distortion product 2f_1-f_2 in normal human ears. J Acoust Soc Am, 1990,89:290
11. Whitehead ML, McCoy MJ, Lonsbuy-Martin BL, et al. Dependence of distortion-product otoacoustic emission on primary levels in normal and impaired ears, I effects of decreasing L_2 below L_1. J Acoust Soc Am, 1995,97:2346-2357
12．廖华，吴展元，周涛等．正常青年人诱发性耳声发射测试．听力学及言语疾病杂志，1997，3：133-137
13. Stover LJ, Neely ST, Gorga MP. Latency and multiple sources of distortion product otoacoustic emission. J Acoust Soc Am, 1996,99:1016
14. Bonfils P, Avon P, Londero A. Objective low frequency audiometry by
distortion-product acoustic emissions.Arch Otolaryngol Head Neck Surg, 1991,117(11):1167-1171
15. Popelka Gr, Osterhammel PA, Nielsen LH. Growth of distortion product otoacoustic emissions with primary-tone level in humans. Hear Res, 1993,71:12-22
16．李克勇，王直中，倪道凤等．士的宁阻断橄榄耳蜗束对豚鼠畸变产物耳声发射的影响．临床耳鼻咽喉科杂志，1998，12(8)：368-369
17. Coffield JA, Miletic V. Immunoreactive enkephalin is contained within some trigeminal and spinal neurons projecting to the rat medial thalamus. Brain Res, 1987,425:380
18. Tanifuji M, Sugiyame T, Murase K. Horizontal propagation of excitation in rat visual cortical slices revealed by optical imaging [J]. Seience, 1994,265(5187): 1057-1059
19. Nelson S, Toth L, Sheth B. Drientation seletivity of cortical neurons during intracellular blockade of inhibition [J]. Science, 1994,265(5173):774-777
20. Benevento LA, Bakkum BN, Cohe RS. Gamma-Aminobutyric acid and somatostatin immunoreactivity in the visual cortex of normal and dark-reared rats [J]. Brain Res, 1995,689(2): 172-182
21. Jeffery AW, David TL, George DP. GABA and Glycine in the central auditory system of the mustache bat: stuctural substrates for inhibitory neuronal organization. J Comp Neurol, 1995.355:317
22. Moore JK, Moore RY. Glutanic acid decarboxylase-like innunoreactivity in brainstem auditory nuclei of the rat. J Comp Neurol, 1987,258:157
23. Suga N. Parallel-hierarchical processing of complex sounds for specialized auditory function. In: Crocker MJ (ed) Encyclopedia of acoustics. Wiley and Sons,New York, 1997,pp1409-1418
24．孔维佳，G. Egg, A. Schrott-Fisher. r-氨基丁酸在人体耳蜗的定位．临床耳鼻咽喉科杂志，1996，10(6)：323-325
25. Wang J, Caspary DM, Salvi RJ. GABA-A antagonist causes dramatic expansion of tuning in primary auditory cortex. Neuroreport, 2000,11:1137-1140
26. William S, Szczepania K, Aage R, et al. Evidence of decreased GABAergic influence on temporal integration in the inferior colliculus following acute noise exposure: a study of evoked potentials in the rat. Neuroscience Letters, 1995,196:77-80
27. J.C. Mibrandt, T.M. Holder, M.C. Wilson, et al. GADlevels and muscimol binding in rat inferior colliculus following acoustic trauma.Hearing Res, 2000,147:251-260
28．周晓明，孙心德．单耳堵塞对蝙蝠下丘GABA阳性反应神经元的影响．[J]生物物理学报，1999，15(1)：218-224
29. XD Sun, Qicai Chen, Philip H-S Jen. Corticofugal control of central auditory sensitivity in the big brown bat, Eptesicus fuscul. Neurosci Letter, 1996,212:131-134
30．徐丽静，孙心德．r-氨基丁酸、谷氨酸等对蝙蝠中脑下丘薄片神经元诱发电活动的影响．生物物理学报，1998，14(3)：473-476
31. Zheng W, Hall JC. GABAergic inhibition shapes frequency tuning and modifies response properties in the superior olivary nucleus of the leopard frog. J Comp Physiol A, 2000.186:661-667
32．储祥平，顾慧珍，徐宁善．r-氨基丁酸对下丘脑腹内侧核神经元单位放电的抑制作用．上海医科大学学报，1998，25(1)：11-14
33. Sapolsky RM. The possibility of neurotoxicity in the hippocampus in major depression: a primer on neuron death. Biol Psychiatry, 2000,48:755-765
34. Harrison RV, Nagasawa A, Smith DW, et al. Reorganization of auditory cortex after neonatal high frequency cochlear hearing loss. Hear Res, 1991,54:11-19
35. Robertson D and Irvine DRF. Plasticity of frequency organization in auditory cortex of guinea pigs partial unilateral deafess. J Comp Neurol, 1989,282:456-471
36. Willott JF and Lu S-M. Noise-induced heating loss can alter neural coding and increase excitability in the central nervous system. Science Wash, 1982,216:1331-1332
37. Jung SC, Shin HC. Suppression of temporary deafferentation-induced plasticity in the primary somatosensory cortex of rats by GABA antagonist. Neurosci Letters, 2002,334(2):87-90
38. Hendry SHC, Jones EG. Reduction in number of immunostained GABAergic neurons in deprived-eye dominance columns of monkey aera. Nature, 1986,320:750-753
39. Tamás G, Buhl EH, Lorinc ZA, et al. Proximally targeted GABAergic synapses and gap junctions synchronize cortical interneurons. Natl Neurosci, 2000,3:366-371
40. Crook JM, Kisvarday ZF, Eyselut. Evidence for a contribution of lateral inhibition to orientation tuning and direction selectivity in cat visual cortex: reversible inactivation of functionally characterized sites combined with neuroanatomical tracing techniques. Eur J Neurosci, 1998,10:2056-2075
41. Kyriaxl HT, Carvell GE, Brumberg JC, et al. Quantitative effects of GABA and bicuculline methiodide on receptive field properties of neurons in real and
simulated whisker barrels. J Neurophysiol, 1996,75:547-560
42. Wang J, Caspary DM, Salvi RJ. GABA-A antagonist causes dramatic expansion of tuning in primary auditory cortex. Neuroreport, 2000,11:1137-1140
43. Levy LM, Ziemann U, Chen R, et al. Rapid modulation of GABA in sensorimotor cortex induced by acute deafferentation. Annals of Neurology, 2002,52(6):755-761
44. Tremere L, Hicks TP, Rasmusson DD. The role of inhibition in cortical reorganization of the adult racoon revealed by microiontophoretic blockade of GABA_A receptors. J Neurophysiol, 2001,86:94-103
45. Chowdhury SA, Rasmusson DD. Comparison of receptive field expansion produced by GABA_B and GABA_A receptor antagonists in racoon primary somatosensory cortex. Exp Brain Res, 2002,144:114-121
46. Cheng X Li, Joseph C, Callaway RS et al. Removal of GABAergic inhibition alters subthreshold input in neurons in forepaw barrel subfield (FBS) in rat first somatosensory cortex (SI) after digit stimulation. Exp Brain Res, 2002,145:411-428
47. Müller CM, Scheich H. GABAergic inhibition increase the neuronal selectivity to natural sounds in the avian auditory forebrain. Brain Res, 1987,414:376-380
48. Schulze H, Langner G. Auditory cortical responses to amplitude modulations with spectra above frequency receptive fields:evidence for wide spectral integration. J Comp Physiol A, 1999,185:493-508
49. Barker JL, Behal T, Li Y-X, et al. GABAergic cells and signals in CNS development. Perspect Dev Neurobiol, 1998,5:305-322
50. Patricia V, Zoya K, Emilia M. GABAsignalling during development: new data and old question. Cell Tissue Res, 2001,305:239-246
2. Robertson D and Irvine DRF. Plasticity of frequency organization in auditory cortex of guinea pigs partial unilateral deafess. J Comp Neurol, 1989,282:456-471
3. Willott JF and Lu S-M. Noise-induced heating loss can alter neural coding and increase excitability in the central nervous system. Science Wash, 1982,216:1331-1332
4. Han MH, Li Y, Yang XL. Desensitizing GABAc receptors on carp retinal bipolar cells. Neuro Report, 1997,8:1331-1335
5. Amin J, Weiss DS. homomeric 1 GABA channels:activation properties and domain. Receptor Channels, 1994,2:227-236
6. Pan ZH, Lipton SA. Multiple GABA receptor subtypes mediate inhibition of calcium influx at rat retinal bipolar cell terminals. J Neurosci, 1995,15:2668-2679
7. Barker JL, Behal T, Li Y-X, et al. GABAergic cells and signals in CNS development. Perspect Dev Neurobiol, 1998,5:305-322
8. Patricia V, Zoya K, Emilia M. GABAsignalling during development: new data and old question. Cell Tissue Res, 2001,305:239-246
9．周晓明，孙心德．单耳堵塞对蝙蝠下丘GABA阳性反应神经元的影响．[J]生物物理学报，1999，15(1)：218-224
10．杨卫平，武文明，方耀云等．老年大鼠耳蜗核r-氨基丁酸免疫反应的变化．中华医学杂志，1998，78(1)：30-32
11. Tamáis G, Buhl EH, Lorinc ZA, et al. Proximally targeted GABAergic synapses and gap junctions synchronize cortical interneurons. Natl Neurosci, 2000,3:366-371
12. Crook JM, Kisvarday ZF, Eyselut. Evidence for a contribution of lateral inhibition to orientation tuning and direction selectivity in cat visual cortex: reversible inactivation of functionally characterized sites combined with neuroanatomical tracing techniques. Eur J Neurosci, 1998,10:2056-2075
13. Kyriaxl HT, Carvell GE, Brumberg JC, et al. Quantitative effects of GABA and bicuculline methiodide on receptive field properties of neurons in real and simulated whisker barrels. J Neurophysiol, 1996,75:547-560
14. Wang J, Caspary DM, Salvi RJ. GABA-A antagonist causes dramatic expansion of
tuning in primary auditory cortex. Neuroreport, 2000,11:1137-1140
1. Kimberley BP, Brown DK, Eggermont JJ. Measuring human cochler travelling wave delay using distortion product emission phase responses. J Acoust Soc Am, 1993,94:1343
2. Martin GR, Ohlms LA, Franklin DJ, et al. Distortion product emission in human Ⅲ, influences of sensorineural loss. Ann Otol Rhinol Laryngol, 1990,99:30
3. Probst R, Lonsbury-martin BL, Martin G. A review of otoacoustic emissions. J Acoust Soc Am, 1991,89:2027
4．哈里逊著，赵月华主译．哈里逊内科学(下册)．神经系统疾病．北京人民卫生出版社，1994，2306-2433
5. S.K. Suneja, S.J. Potashner, C.G. Benson. Plastic changes in Glycine and GABA release and uptake in adult brainstem auditory nuclei after unilateral middle ear ossicle removal and cochlear ablation. Experimental neurology, 1998,151:273-288
6. Catherine DW, Gérard L, Antonio CT, et al. Lack of growth-associated protein-43 reemergence or of growth-associated protein-43 mRNA modulation in deafferented vestibular nuclei during the first 6 weeks after nuilateral inner ear lesion.Exp Brain Res, 2000,132:464-475
7. Smurzynski J, Kim DO. Distortion-product and click-evoked otoacoustic emission of normally hearing adults. Hear Res, 1992,58:227-240
8. Lonsbury-Martin BL, Martin GK. The clinical application of acoustic distortion products. Otolaryngol Head-Neck Surgery, 1990,103:52
9. Dallos P.The active cochlear. J Neuro Sci, 1992,12(2):4575-4585
10. Hauser R, Probest R. The influence of systematic primary-tone level variation L_1-L_2 on the acoustic distortion product 2f_1-f_2 in normal human ears. J Acoust Soc Am, 1990,89:290
11. Whitehead ML, McCoy MJ, Lonsbuy-Martin BL, et al. Dependence of distortion-product otoacoustic emission on primary levels in normal and impaired ears, I effects of decreasing L_2 below L_1. J Acoust Soc Am, 1995,97:2346-2357
12．廖华，吴展元，周涛等．正常青年人诱发性耳声发射测试．听力学及言语疾病杂志，1997，3：133-137
13. Stover LJ, Neely ST, Gorga MP. Latency and multiple sources of distortion product otoacoustic emission. J Acoust Soc Am, 1996,99:1016
14. Bonfils P, Avon P, Londero A. Objective low frequency audiometry by
distortion-product acoustic emissions.Arch Otolaryngol Head Neck Surg, 1991,117(11):1167-1171
15. Popelka Gr, Osterhammel PA, Nielsen LH. Growth of distortion product otoacoustic emissions with primary-tone level in humans. Hear Res, 1993,71:12-22
16．李克勇，王直中，倪道凤等．士的宁阻断橄榄耳蜗束对豚鼠畸变产物耳声发射的影响．临床耳鼻咽喉科杂志，1998，12(8)：368-369
17. Coffield JA, Miletic V. Immunoreactive enkephalin is contained within some trigeminal and spinal neurons projecting to the rat medial thalamus. Brain Res, 1987,425:380
18. Tanifuji M, Sugiyame T, Murase K. Horizontal propagation of excitation in rat visual cortical slices revealed by optical imaging [J]. Seience, 1994,265(5187): 1057-1059
19. Nelson S, Toth L, Sheth B. Drientation seletivity of cortical neurons during intracellular blockade of inhibition [J]. Science, 1994,265(5173):774-777
20. Benevento LA, Bakkum BN, Cohe RS. Gamma-Aminobutyric acid and somatostatin immunoreactivity in the visual cortex of normal and dark-reared rats [J]. Brain Res, 1995,689(2): 172-182
21. Jeffery AW, David TL, George DP. GABA and Glycine in the central auditory system of the mustache bat: stuctural substrates for inhibitory neuronal organization. J Comp Neurol, 1995.355:317
22. Moore JK, Moore RY. Glutanic acid decarboxylase-like innunoreactivity in brainstem auditory nuclei of the rat. J Comp Neurol, 1987,258:157
23. Suga N. Parallel-hierarchical processing of complex sounds for specialized auditory function. In: Crocker MJ (ed) Encyclopedia of acoustics. Wiley and Sons,New York, 1997,pp1409-1418
24．孔维佳，G. Egg, A. Schrott-Fisher. r-氨基丁酸在人体耳蜗的定位．临床耳鼻咽喉科杂志，1996，10(6)：323-325
25. Wang J, Caspary DM, Salvi RJ. GABA-A antagonist causes dramatic expansion of tuning in primary auditory cortex. Neuroreport, 2000,11:1137-1140
26. William S, Szczepania K, Aage R, et al. Evidence of decreased GABAergic influence on temporal integration in the inferior colliculus following acute noise exposure: a study of evoked potentials in the rat. Neuroscience Letters, 1995,196:77-80
27. J.C. Mibrandt, T.M. Holder, M.C. Wilson, et al. GADlevels and muscimol binding in rat inferior colliculus following acoustic trauma.Hearing Res, 2000,147:251-260
28．周晓明，孙心德．单耳堵塞对蝙蝠下丘GABA阳性反应神经元的影响．[J]生物物理学报，1999，15(1)：218-224
29. XD Sun, Qicai Chen, Philip H-S Jen. Corticofugal control of central auditory sensitivity in the big brown bat, Eptesicus fuscul. Neurosci Letter, 1996,212:131-134
30．徐丽静，孙心德．r-氨基丁酸、谷氨酸等对蝙蝠中脑下丘薄片神经元诱发电活动的影响．生物物理学报，1998，14(3)：473-476
31. Zheng W, Hall JC. GABAergic inhibition shapes frequency tuning and modifies response properties in the superior olivary nucleus of the leopard frog. J Comp Physiol A, 2000.186:661-667
32．储祥平，顾慧珍，徐宁善．r-氨基丁酸对下丘脑腹内侧核神经元单位放电的抑制作用．上海医科大学学报，1998，25(1)：11-14
33. Sapolsky RM. The possibility of neurotoxicity in the hippocampus in major depression: a primer on neuron death. Biol Psychiatry, 2000,48:755-765
34. Harrison RV, Nagasawa A, Smith DW, et al. Reorganization of auditory cortex after neonatal high frequency cochlear hearing loss. Hear Res, 1991,54:11-19
35. Robertson D and Irvine DRF. Plasticity of frequency organization in auditory cortex of guinea pigs partial unilateral deafess. J Comp Neurol, 1989,282:456-471
36. Willott JF and Lu S-M. Noise-induced heating loss can alter neural coding and increase excitability in the central nervous system. Science Wash, 1982,216:1331-1332
37. Jung SC, Shin HC. Suppression of temporary deafferentation-induced plasticity in the primary somatosensory cortex of rats by GABA antagonist. Neurosci Letters, 2002,334(2):87-90
38. Hendry SHC, Jones EG. Reduction in number of immunostained GABAergic neurons in deprived-eye dominance columns of monkey aera. Nature, 1986,320:750-753
39. Tamás G, Buhl EH, Lorinc ZA, et al. Proximally targeted GABAergic synapses and gap junctions synchronize cortical interneurons. Natl Neurosci, 2000,3:366-371
40. Crook JM, Kisvarday ZF, Eyselut. Evidence for a contribution of lateral inhibition to orientation tuning and direction selectivity in cat visual cortex: reversible inactivation of functionally characterized sites combined with neuroanatomical tracing techniques. Eur J Neurosci, 1998,10:2056-2075
41. Kyriaxl HT, Carvell GE, Brumberg JC, et al. Quantitative effects of GABA and bicuculline methiodide on receptive field properties of neurons in real and
simulated whisker barrels. J Neurophysiol, 1996,75:547-560
42. Wang J, Caspary DM, Salvi RJ. GABA-A antagonist causes dramatic expansion of tuning in primary auditory cortex. Neuroreport, 2000,11:1137-1140
43. Levy LM, Ziemann U, Chen R, et al. Rapid modulation of GABA in sensorimotor cortex induced by acute deafferentation. Annals of Neurology, 2002,52(6):755-761
44. Tremere L, Hicks TP, Rasmusson DD. The role of inhibition in cortical reorganization of the adult racoon revealed by microiontophoretic blockade of GABA_A receptors. J Neurophysiol, 2001,86:94-103
45. Chowdhury SA, Rasmusson DD. Comparison of receptive field expansion produced by GABA_B and GABA_A receptor antagonists in racoon primary somatosensory cortex. Exp Brain Res, 2002,144:114-121
46. Cheng X Li, Joseph C, Callaway RS et al. Removal of GABAergic inhibition alters subthreshold input in neurons in forepaw barrel subfield (FBS) in rat first somatosensory cortex (SI) after digit stimulation. Exp Brain Res, 2002,145:411-428
47. Müller CM, Scheich H. GABAergic inhibition increase the neuronal selectivity to natural sounds in the avian auditory forebrain. Brain Res, 1987,414:376-380
48. Schulze H, Langner G. Auditory cortical responses to amplitude modulations with spectra above frequency receptive fields:evidence for wide spectral integration. J Comp Physiol A, 1999,185:493-508
49. Barker JL, Behal T, Li Y-X, et al. GABAergic cells and signals in CNS development. Perspect Dev Neurobiol, 1998,5:305-322
50. Patricia V, Zoya K, Emilia M. GABAsignalling during development: new data and old question. Cell Tissue Res, 2001,305:239-246