Diminished cortical inhibition in an aging mouse model of chronic tinnitus.
Diminished cortical inhibition in an aging mouse model of chronic tinnitus.
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DOI：
10.1523/jneurosci.2499-12.2012
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发表时间：
2012-11-14
期刊：
影响因子：
--
通讯作者：
Caspary DM
中科院分区：
文献类型：
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作者：
Llano DA;Turner J;Caspary DM
用黄素蛋白自发荧光成像技术检测了有耳鸣和听力损失行为证据的老年动物的听觉皮层突触反应。在1- 3月龄时将小鼠暴露于噪声创伤，在噪声创伤后立即评估耳鸣和听力损失的行为证据，并在大约24-30月龄时再次评估。在最终行为评估的两个月内，使用假定的丘脑皮质传入的电刺激在脑切片中检查听觉皮质突触传递，并使用黄素蛋白自体荧光成像来测量皮质激活。与对照组相比，噪声暴露动物的皮质激活幅度增加了68%（p=0.008），这些动物对GABAA能阻断的敏感性降低（p=0.008，使用浴用200 nM SR 95531）。皮层激活的强度与耳鸣行为的程度显著相关，通过惊吓范例中的间隙检测损失进行评估。GABAA敏感性的降低在远离刺激部位的皮质区域中更大，可能反映了皮质皮质与丘脑皮质投射对噪声创伤影响的更大敏感性。最后，在相同的切片中，听觉皮层激活和体感皮层激活之间没有关系，这表明听觉皮层激活的增加不是由于噪声暴露动物的普遍过度兴奋状态。这些数据表明，噪声创伤可以引起听觉皮层生理学的长期变化，并可能提供特定的目标，以改善慢性耳鸣的影响。
Flavoprotein autofluorescence imaging was used to examine auditory cortical synaptic responses in aged animals with behavioral evidence of tinnitus and hearing loss. Mice were exposed to noise trauma at 1–3months of age, were assessed for behavioral evidence of tinnitus and hearing loss immediately after the noise trauma and again at approximately 24–30 months of age. Within two months of the final behavioral assessment, auditory cortical synaptic transmission was examined in brain slices using electrical stimulation of putative thalamocortical afferents, and flavoprotein autofluorescence imaging was used to measure cortical activation. Noise-exposed animals showed a 68% increase in amplitude of cortical activation compared to controls (p=0.008), and these animals showed a diminished sensitivity to GABAA ergic blockade (p=0.008, using bath-applied 200 nM SR 95531). The strength of cortical activation was significantly correlated to the degree of tinnitus behavior, assessed via a loss of gap detection in a startle paradigm. The decrease in GABAA sensitivity was greater in the regions of the cortex further away from the stimulation site, potentially reflecting a greater sensitivity of corticocortical vs. thalamocortical projections to the effects of noise trauma. Finally, there was no relationship between auditory cortical activation and activation of the somatosensory cortex in the same slices, suggesting that the increases in auditory cortical activation were not due to a generalized hyperexcitable state in noise-exposed animals. These data suggest that noise trauma can cause long-lasting changes in the auditory cortical physiology and may provide specific targets to ameliorate the effects of chronic tinnitus.