The Nature and Origin of Synaptic Inputs to Vestibulospinal Neurons in the Larval Zebrafish.

The Nature and Origin of Synaptic Inputs to Vestibulospinal Neurons in the Larval Zebrafish.
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DOI:
10.1523/eneuro.0090-23.2023
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发表时间:
2023-06
期刊:
影响因子:
3.4
通讯作者:
--
中科院分区:
医学3区
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前庭脊髓神经元整合感觉到的不平衡来调节姿势反射。作为一个进化保守的神经群体,了解它们的突触和电路水平的属性可以提供深入了解脊椎动物的反重力反射。最近的工作的动机,我们着手验证和扩展的特征前庭脊髓神经元的幼体斑马鱼。使用电流钳记录与刺激一起,我们观察到,幼虫斑马鱼前庭脊髓神经元在休息时是沉默的,但能够持续尖峰以下去极化。神经元对前庭刺激(黑暗中的翻译)有系统的反应;在椭圆囊耳石慢性或急性丧失后,反应被取消。休息时的电压钳记录显示了强烈的兴奋性输入与特征的多峰分布的振幅,以及强抑制性输入。兴奋性输入在一个特定的模式(幅度范围)经常违反不应期标准,并表现出复杂的感觉调谐,这表明一个非单一的起源。接下来,使用单侧功能丧失的方法,我们表征了来自每只耳朵的前庭脊髓神经元的前庭输入的来源。我们观察到系统性的损失后,椭圆囊病变同侧,但不是对侧,记录前庭脊髓神经元的高振幅兴奋性输入。相反,虽然一些神经元在同侧或对侧损伤后抑制性输入减少,但在记录的神经元群体中没有系统性变化。我们的结论是,不平衡的椭圆囊耳石形状的幼虫斑马鱼前庭脊髓神经元的反应,通过兴奋性和抑制性输入。我们的研究结果扩展了我们对脊椎动物模型(斑马鱼幼体)如何使用前庭脊髓输入来稳定姿势的理解。更广泛地说,当与其他脊椎动物的记录相比,我们的数据说话的前庭脊髓突触输入保守的起源。
Vestibulospinal neurons integrate sensed imbalance to regulate postural reflexes. As an evolutionarily conserved neural population, understanding their synaptic and circuit-level properties can offer insight into vertebrate antigravity reflexes. Motivated by recent work, we set out to verify and extend the characterization of vestibulospinal neurons in the larval zebrafish. Using current-clamp recordings together with stimulation, we observed that larval zebrafish vestibulospinal neurons are silent at rest, yet capable of sustained spiking following depolarization. Neurons responded systematically to a vestibular stimulus (translation in the dark); responses were abolished after chronic or acute loss of the utricular otolith. Voltage-clamp recordings at rest revealed strong excitatory inputs with a characteristic multimodal distribution of amplitudes, as well as strong inhibitory inputs. Excitatory inputs within a particular mode (amplitude range) routinely violated refractory period criteria and exhibited complex sensory tuning, suggesting a nonunitary origin. Next, using a unilateral loss-of-function approach, we characterized the source of vestibular inputs to vestibulospinal neurons from each ear. We observed systematic loss of high-amplitude excitatory inputs after utricular lesions ipsilateral, but not contralateral, to the recorded vestibulospinal neuron. In contrast, while some neurons had decreased inhibitory inputs after either ipsilateral or contralateral lesions, there were no systematic changes across the population of recorded neurons. We conclude that imbalance sensed by the utricular otolith shapes the responses of larval zebrafish vestibulospinal neurons through both excitatory and inhibitory inputs. Our findings expand our understanding of how a vertebrate model, the larval zebrafish, might use vestibulospinal input to stabilize posture. More broadly, when compared with recordings in other vertebrates, our data speak to conserved origins of vestibulospinal synaptic input.