Nonquantal transmission at the vestibular hair cell-calyx synapse: K(LV) currents modulate fast electrical and slow K(+) potentials.

Nonquantal transmission at the vestibular hair cell-calyx synapse: K(LV) currents modulate fast electrical and slow K(+) potentials.
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DOI:
10.1073/pnas.2207466120
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发表时间:
2023-01-10
影响因子:
11.1
通讯作者:
--
中科院分区:
综合性期刊1区
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前庭系统驱动神经系统最快反射的能力依赖于前庭毛细胞突触机械感觉信号的快速传递。在哺乳动物和其他羊膜动物中,传入神经元在某些毛细胞上形成异常大的花萼终末,这些突触的沟通包括非量子传递(NQT),这避免了量子传递的突触延迟。我们提出了一个定量模型,说明了NQT如何依赖于毛细胞被花瓣覆盖的程度,并将NQT的短潜伏期归因于通过毛细胞中开放的钾通道的电流引起的突触裂隙电位的变化。这种细胞间的电传递机制可能作用于其他突触。前庭毛细胞通过突触向初级传入神经元传递有关头部位置和运动的信息。在其中一些突触,传入神经元包裹毛细胞,形成一个扩大的突触末端,称为花冠。前庭毛细胞-花冠突触支持一种神秘的不涉及缝隙连接的电传递形式,称为非量子传递(NQT)。NQT机制被认为涉及到离子从突触前毛细胞通过低电压激活的通道从突触前毛细胞流向突触后毛细胞,这种通道是由K+退出毛细胞时裂隙[K+]的变化驱动的。然而,这一假设还没有得到定量模型的检验,而且电势在裂隙中可能扮演的角色仍然是推测的。在这里,我们提出了一个计算模型,捕获了对NQT的实验观察,并确定了支持突触间隙中存在电势(ϕ)的特征。我们发现,裂隙ϕ的改变减少了传输延迟,并说明了裂隙[K+]和ϕ对NQT的增益和相位的相对贡献。我们进一步证明,NQT的大小和速度取决于花萼的形态,并且增加花瓣高度可以减少花瓣传入的动作电位潜伏期。这些预测与花萼进化以增强NQT和加速前庭信号的想法是一致的,前庭信号驱动控制凝视、平衡和方向的神经回路。
The ability of the vestibular system to drive the fastest reflexes in the nervous system depends on rapid transmission of mechanosensory signals at vestibular hair cell synapses. In mammals and other amniotes, afferent neurons form unusually large calyx terminals on certain hair cells, and communication at these synapses includes nonquantal transmission (NQT), which avoids the synaptic delay of quantal transmission. We present a quantitative model that shows how NQT depends on the extent of the calyx covering the hair cell and attributes the short latency of NQT to changes in synaptic cleft electrical potential caused by current flowing through open potassium channels in the hair cell. This mechanism of electrical transmission between cells may act at other synapses. Vestibular hair cells transmit information about head position and motion across synapses to primary afferent neurons. At some of these synapses, the afferent neuron envelopes the hair cell, forming an enlarged synaptic terminal called a calyx. The vestibular hair cell–calyx synapse supports a mysterious form of electrical transmission that does not involve gap junctions, termed nonquantal transmission (NQT). The NQT mechanism is thought to involve the flow of ions from the presynaptic hair cell to the postsynaptic calyx through low-voltage-activated channels driven by changes in cleft [K+] as K+ exits the hair cell. However, this hypothesis has not been tested with a quantitative model and the possible role of an electrical potential in the cleft has remained speculative. Here, we present a computational model that captures experimental observations of NQT and identifies features that support the existence of an electrical potential (ϕ) in the synaptic cleft. We show that changes in cleft ϕ reduce transmission latency and illustrate the relative contributions of both cleft [K+] and ϕ to the gain and phase of NQT. We further demonstrate that the magnitude and speed of NQT depend on calyx morphology and that increasing calyx height reduces action potential latency in the calyx afferent. These predictions are consistent with the idea that the calyx evolved to enhance NQT and speed up vestibular signals that drive neural circuits controlling gaze, balance, and orientation.
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