Neural Basis of Audio-Vocal Integration

描述（由申请人提供）：这里的主要目标是检查控制哺乳动物发声以响应脑干中的听觉反馈的神经元底物和机制。重点分析了两个区域：（1）臂旁核（PB），和（2）喉控制运动核-疑核（NA）。他们的作用听觉反馈控制发声将在清醒的，行为马蹄蝙蝠。这些蝙蝠通过听觉反馈准确地控制它们的回声定位呼叫的频率，无论是在蝙蝠休息时（休息频率，RF），还是在飞行时，都能补偿频移回声信号（多普勒频移补偿，DSC）。药理学研究表明，PB是必不可少的控制，RF和DSC和确定的发射机参与。该项目有两个具体目标：第一，研究PB的听觉-发声控制的神经机制和解剖学联系。为此，将通过电子回放在自发发声的静止动物中引发DSC行为，并持续监测。将使用立体定位坐标定位PB，并确定神经活性药物注射对DSC和RF产生最大影响的区域。随后在该区域的细胞外单单位记录将与听觉反馈和由此产生的呼叫频率变化相关。同时注射递质激动剂和拮抗剂将允许将神经元活动的变化与行为中观察到的变化联系起来。PB的顺向和逆向投射模式将通过将神经示踪剂离子导入PB来确定。第二，研究NA是如何参与听觉反馈控制的呼叫频率。将采用与PB相同的药理学、神经生理学和解剖学方法：测试各种兴奋性和抑制性激动剂和拮抗剂对RF和DSC的影响，随后进行细胞外单单位记录，并分析解剖学连接。这些研究的结果将产生新的见解神经元实现的声音控制机制在清醒的，行为的动物准备。它们还具有更好地理解人类各种心理声学现象的神经机制的潜力，例如对音高变化反馈的非自愿反应，以及人类语音基本参数的各种故障，例如在说话的聋人中发生的基频变化。

DESCRIPTION (provided by applicant): The chief goal here is to examine the neuronal substrates and mechanisms that control mammalian sound production in response to auditory feedback in the brainstem. Focus is on the analysis of two areas: (1) the parabrachial nucleus (PB), and (2), the motor nucleus of laryngeal control, nucleus ambiguus (NA). Their role for auditory feedback control of vocalizations will be tested in awake, behaving horseshoe bats. These bats accurately control the frequency of their echolocation calls through auditory feedback both when the bat is at rest (resting frequency, RF) and when it is flying and compensating for frequency-shifted echo signals (Doppler-shift compensation, DSC). Pharmacological studies showed that PB is essential for the control of both, RF and DSC and identified the transmitters involved. The proposed project has two specific aims: First, to examine the neuronal mechanism(s) and the anatomical connections underlying this audio-vocal control by the PB. For that purpose, DSC behavior will be elicited in spontaneously vocalizing, stationary animals by electronic playback and constantly be monitored. The PB will be localized using stereotaxic coordinates and the area determined where injections of neuroactive agents yield maximum effects on DSC and RF. Subsequent extracellular single-unit recordings in this area will be correlated with both the auditory feedback and resulting changes in call frequency. Simultaneous injections of transmitter agonists and antagonists will allow to relate changes in neuronal activity to the changes observed in the behavior. The antero- and retrograde projection patterns of PB will be determined by iontophoresis of neurotracers into PB. Second, to investigate how NA is involved in auditory feedback control of call frequencies. The same combined pharmacological, neurophysiological, and anatomical approach will be taken as for PB: tests of the effects of various excitatory and inhibitory agonists and antagonists on RF and DSC, subsequent extracellular single-unit recordings, and analysis of anatomical connectivity. The results of these studies will yield new insights into the neuronal implementation of audio-vocal control mechanisms in an awake, behaving animal preparation. They also bear the potential to provide a better understanding of the neuronal mechanisms of various psychoacoustic phenomena in humans, e.g. the involuntary response to pitch-shifted feedback, and various malfunctions of basic parameters of human voice, such as changes in the fundamental frequency that occur in speaking deaf humans.