Targeted Training of Ultrasonic Vocalizations in Aged and Parkinsonian Rats
Targeted Training of Ultrasonic Vocalizations in Aged and Parkinsonian Rats
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DOI：
10.3791/2835
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发表时间：
2011-08-01
影响因子：
1.2
通讯作者：
Ciucci, Michelle R.
中科院分区：
文献类型：
--
作者：
Johnson, Aaron M.;Doll, Emerald J.;Ciucci, Michelle R.
语音缺陷是帕金森病（PD）和衰老的常见并发症;它们可以通过影响沟通能力显着降低生活质量。（1，2）有针对性的训练（言语/声音治疗）可以改善特定的声音缺陷，（3，4）尽管行为干预的潜在机制还不清楚。声音缺陷的系统研究和治疗应考虑许多人类难以控制的因素，如年龄、家庭环境、发病后年龄、疾病严重程度和药物治疗。这里提出的方法使用发声的动物模型，允许系统地研究潜在的感觉运动机制如何随着有针对性的语音训练而改变。本方案中概述的超声记录和分析程序适用于啮齿动物超声发声的任何研究。啮齿动物的超声发声正在成为研究行为神经基础的有价值的模型。(5-8)啮齿类动物和人类的发声都具有符号学价值，并且是通过用喉部收缩来改变流出的气流而产生的。（9，10）因此，啮齿动物的发声可能是一个有用的模型，以研究语音缺陷的感觉运动背景。此外，大鼠模型使我们能够研究通过有针对性的训练从缺陷中恢复的神经生物学基础。并通过向内侧前脑束单侧输注7 μ g 6-羟基多巴胺（6-OHDA）诱导帕金森综合征，这导致突触前纹状体神经元中度至重度变性（详情参见Ciucci，2010）。(11)对于我们的衰老模型，我们使用Fischer 344/Brown Norway F1（国家衰老研究所）。我们引发发声的主要方法是将有性经验的雄性大鼠暴露于性接受的雌性大鼠。当雄性对雌性感兴趣时，雌性被带走，雄性继续发声。通过食物或水奖励复杂的发声，可以增加复杂发声的数量和发声的速度（图1）。安装在雄性笼子上方的超声波麦克风记录发声。记录开始后，雌性大鼠被删除，以隔离男性的呼吁。发声可以在真实的时间进行训练或离线记录和分析。通过记录和声学分析发声训练前后的发声，可以评估疾病的影响和训练后正常功能的恢复。这个模型还允许我们将观察到的行为（声音）改善与大脑和神经肌肉系统的变化联系起来。
Voice deficits are a common complication of both Parkinson disease (PD) and aging; they can significantly diminish quality of life by impacting communication abilities. (1, 2) Targeted training (speech/voice therapy) can improve specific voice deficits, (3, 4) although the underlying mechanisms of behavioral interventions are not well understood. Systematic investigation of voice deficits and therapy should consider many factors that are difficult to control in humans, such as age, home environment, age post-onset of disease, severity of disease, and medications. The method presented here uses an animal model of vocalization that allows for systematic study of how underlying sensorimotor mechanisms change with targeted voice training. The ultrasonic recording and analysis procedures outlined in this protocol are applicable to any investigation of rodent ultrasonic vocalizations.The ultrasonic vocalizations of rodents are emerging as a valuable model to investigate the neural substrates of behavior.(5-8) Both rodent and human vocalizations carry semiotic value and are produced by modifying an egressive airflow with a laryngeal constriction. (9, 10) Thus, rodent vocalizations may be a useful model to study voice deficits in a sensorimotor context. Further, rat models allow us to study the neurobiological underpinnings of recovery from deficits with targeted training.To model PD we use Long-Evans rats (Charles River Laboratories International, Inc.) and induce parkinsonism by a unilateral infusion of 7 mu g of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle which causes moderate to severe degeneration of presynaptic striatal neurons (for details see Ciucci, 2010). (11), (12) For our aging model we use the Fischer 344/Brown Norway F1 (National Institute on Aging).Our primary method for eliciting vocalizations is to expose sexually-experienced male rats to sexually receptive female rats. When the male becomes interested in the female, the female is removed and the male continues to vocalize. By rewarding complex vocalizations with food or water, both the number of complex vocalizations and the rate of vocalizations can be increased (Figure 1).An ultrasonic microphone mounted above the male's home cage records the vocalizations. Recording begins after the female rat is removed to isolate the male calls. Vocalizations can be viewed in real time for training or recorded and analyzed offline. By recording and acoustically analyzing vocalizations before and after vocal training, the effects of disease and restoration of normal function with training can be assessed. This model also allows us to relate the observed behavioral (vocal) improvements to changes in the brain and neuromuscular system.