PDF(Pubmed)
Abstract：
The encoding of acoustic stimuli requires precise neuron timing. Auditory neurons in the cochlear nucleus (CN) and brainstem are well suited for accurate analysis of fast acoustic signals, given their physiological specializations of fast membrane time constants, fast axonal conduction, and reliable synaptic transmission. The medial olivocochlear (MOC) neurons that provide efferent inhibition of the cochlea reside in the ventral brainstem and participate in these fast neural circuits. However, their modulation of cochlear function occurs over time scales of a slower nature. This suggests the presence of mechanisms that reduce MOC inhibition of cochlear function. To determine how monaural excitatory and inhibitory synaptic inputs integrate to affect the timing of MOC neuron activity, we developed a novel in vitro slice preparation (\"wedge-slice\"). The wedge-slice maintains the ascending auditory nerve root, the entire CN and projecting axons, while preserving the ability to perform visually guided patch-clamp electrophysiology recordings from genetically identified MOC neurons. The \"in vivo-like\" timing of the wedge-slice demonstrates that the inhibitory pathway accelerates relative to the excitatory pathway when the ascending circuit is intact, and the CN portion of the inhibitory circuit is precise enough to compensate for reduced precision in later synapses. When combined with machine learning PSC analysis and computational modeling, we demonstrate a larger suppression of MOC neuron activity when the inhibition occurs with in vivo-like timing. This delay of MOC activity may ensure that the MOC system is only engaged by sustained background sounds, preventing a maladaptive hypersuppression of cochlear activity.
摘要：
声刺激的编码需要精确的神经元定时。耳蜗核（CN）和脑干中的听觉神经元非常适合准确分析快速声学信号，鉴于他们对快速膜时间常数的生理专长，快速轴突传导,和可靠的突触传递.提供耳蜗传出抑制的内侧橄榄耳蜗（MOC）神经元位于腹侧脑干中，并参与这些快速神经回路。然而,它们对耳蜗功能的调节发生在较慢性质的时间尺度上。这表明存在降低MOC抑制耳蜗功能的机制。为了确定单耳兴奋性和抑制性突触输入如何整合以影响MOC神经元活动的时间，我们开发了一种新型的体外切片制备方法(“楔形切片”)。楔形切片保持上升的听觉神经根，整个CN和突出的轴突，同时保留了从遗传鉴定的MOC神经元进行视觉引导的膜片钳电生理记录的能力。楔形切片的“体内样”时序表明，当上升回路完好无损时，抑制途径相对于兴奋性途径加速，并且抑制性电路的CN部分精确到足以补偿后期突触中降低的精度。当与机器学习PSC分析和计算建模相结合时，当抑制发生在体内时，我们证明了MOC神经元活性的更大抑制。MOC活动的这种延迟可能会确保MOC系统仅由持续的背景声音参与，防止适应不良的耳蜗活动过度抑制。重要性声明听觉脑干神经元专门用于速度和保真度，以编码声音的快速特征。极快的抑制有助于精确的脑干声音编码。该电路还投射到抑制耳蜗功能的内侧橄榄耳蜗（MOC）传出神经元，以增强对背景声音中信号的检测。使用具有完整上升电路的新型脑切片制剂，我们表明MOC神经元的抑制也可以非常快，电路的速度定位于耳蜗核。与其他脑干听觉回路的快速抑制所提供的精度增强相反，相反，对MOC神经元的抑制具有延迟和去同步活动的可变发作，从而降低了慢速的精度，对背景声音的持续反应。
