Hamling Kyla R, Harmon Katherine, Schoppik David
Departments of Otolaryngology, Neuroscience & Physiology, and the Neuroscience Institute, New York University Grossman School of Medicine.
bioRxiv. 2023 Mar 16:2023.03.15.532859. doi: 10.1101/2023.03.15.532859.
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 non-unitary 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 to 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失衡以调节姿势反射。作为一个在进化上保守的神经群体，了解它们的突触和回路水平特性可以为脊椎动物的抗重力反射提供见解。受近期研究工作的推动，我们着手验证并扩展对幼体斑马鱼前庭脊髓神经元的特性描述。通过使用电流钳记录结合刺激，我们观察到幼体斑马鱼前庭脊髓神经元在静息时是沉默的，但在去极化后能够持续发放动作电位。神经元对前庭刺激（在黑暗中平移）有系统性反应；在内耳椭圆囊耳石慢性或急性缺失后，反应消失。静息时的电压钳记录显示有强大的兴奋性输入，其幅度具有特征性的多峰分布，以及强大的抑制性输入。特定模式（幅度范围）内的兴奋性输入经常违反不应期标准，并表现出复杂的感觉调谐，这表明其来源并非单一。接下来，我们采用单侧功能缺失方法，对来自每只耳朵的前庭脊髓神经元的前庭输入来源进行了特性描述。我们观察到，与记录的前庭脊髓神经元同侧但非对侧的椭圆囊损伤后，高幅度兴奋性输入出现系统性缺失。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性变化。我们得出结论，椭圆囊耳石感知到的失衡通过兴奋性和抑制性输入塑造了幼体斑马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体斑马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，我们的数据表明前庭脊髓突触输入具有保守的起源。
