Neural Basis of Audio-Vocal Integration

描述(申请人提供)：这里的主要目标是研究控制哺乳动物声音产生的神经元底物和机制，以响应脑干中的听觉反馈。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)。它们在发声的听觉反馈控制中的作用将在清醒的马蹄蝙蝠身上进行测试。这些蝙蝠通过听觉反馈精确控制其回声定位叫声的频率，无论是在蝙蝠静止时(静止频率，RF)，还是在飞行时，并补偿频移的回声信号(多普勒频移补偿，DSC)。药理学研究表明，PB对RF和DSC的控制都是必不可少的，并确定了涉及的递质。拟议的项目有两个具体目标：第一，研究神经元机制(S)和PB控制音频-声音的解剖学联系。为此，DSC行为将通过电子回放在自发发声的静止动物中诱导出来，并不断受到监控。将使用立体定位坐标定位PB，并确定注射神经活性物质对DSC和RF产生最大影响的区域。这一区域随后的细胞外单个单元录音将与听觉反馈和由此导致的呼叫频率变化相关联。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观察到的行为变化联系起来。PB的前向和逆行投射模式将通过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呼叫频率的。对于PB，将采取相同的药理学、神经生理学和解剖学相结合的方法：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，并分析解剖连接。这些研究的结果将为清醒的、行为的动物准备中听觉-发声控制机制的神经元实现提供新的见解。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，例如对音调变化的反馈的非自愿反应，以及人类声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.