Departments of Otolaryngology and Neuroscience & Physiology, and Neuroscience Institute, New York University Grossman School of Medicine, New York, New York 10016.
Departments of Otolaryngology and Neuroscience & Physiology, and Neuroscience Institute, New York University Grossman School of Medicine, New York, New York 10016
eNeuro. 2023 Jun 2;10(6). doi: 10.1523/ENEURO.0090-23.2023. Print 2023 Jun.
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.
前庭脊髓神经元整合感知到的不平衡,以调节姿势反射。作为一个进化上保守的神经元群体,了解它们的突触和电路水平特性可以深入了解脊椎动物抗重力反射。受最近研究的启发,我们着手验证并扩展对幼鱼前庭脊髓神经元的描述。我们使用电流钳记录和刺激相结合的方法,观察到幼鱼前庭脊髓神经元在静止时处于沉默状态,但在去极化后能够持续产生尖峰。神经元对前庭刺激(在黑暗中平移)做出系统响应;在慢性或急性丧失耳石后,反应被消除。在静息状态下的电压钳记录显示,兴奋性输入很强,具有特征性的多模态幅度分布,以及强烈的抑制性输入。在特定模式(幅度范围)内的兴奋性输入通常违反不应期标准,并表现出复杂的感觉调谐,表明其具有非单元起源。接下来,我们使用单侧功能丧失方法,从每只耳朵描述前庭输入到前庭脊髓神经元的来源。我们观察到在记录的前庭脊髓神经元同侧的耳石损伤后,高幅度兴奋性输入有系统地丧失,但在对侧没有丧失。相比之下,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变化。我们得出结论,耳石感觉到的不平衡通过兴奋性和抑制性输入来塑造幼鱼前庭脊髓神经元的反应。我们的发现扩展了我们对脊椎动物模型(幼鱼)如何利用前庭脊髓输入来稳定姿势的理解。更广泛地说,与其他脊椎动物的记录相比,我们的数据表明了前庭脊髓突触输入的保守起源。