Department of Biomedical Science, University of Sheffield, Sheffield, UK.
Neuroscience Institute, University of Sheffield, Sheffield, UK.
J Physiol. 2021 Aug;599(15):3677-3696. doi: 10.1113/JP281646. Epub 2021 Jul 9.
The present study aimed to determine the sensory adaptation characteristics of hair cell ribbon synapses in vivo. Hair cells of the zebrafish lateral line transmit hydrodynamic stimuli to the posterior lateral line ganglion afferent neurons. Excitatory hair bundle deflections by water-jet stimuli cause glutamate release at hair cell synapses with a rapid (phasic) and a sustained component, which are likely linked to the exocytosis of distinct vesicle pools. The glutamate-induced increase in afferent neuron firing rate adapts over time, which is mirrored by the depression of neurotransmitter release, without preventing phase-locking. Adaptation also occurs during inhibitory hair bundle displacements, highlighting a shift in the sensitivity range of the lateral line during prolonged stimulation. Postsynaptic mechanisms exert some degree of regulation on the afferent firing adaptation. We conclude that vesicle depletion is the primary determinant of firing rate adaptation, allowing lateral line hair cell ribbon synapses to maintain sensitivity to sustained stimuli.
Adaptation is used by sensory systems to adjust continuously their sensitivity to match changes in environmental stimuli. In the auditory and vestibular systems, the release properties of glutamate-containing vesicles at the hair cell ribbon synapses play a crucial role in sensory adaptation, thus shaping the neural response to sustained stimulation. How ribbon synapses regulate the release of glutamate and how they modulate afferent responses in vivo is still largely unknown. Here, we have used two-photon imaging and electrophysiology to investigate the synaptic transfer characteristics of the hair cells in the context of sensory adaptation in live zebrafish. Prolonged and repeated water-jet stimulation of the hair cell stereociliary bundles caused adaptation of the action potential firing rate elicited in the afferent neurons. By monitoring glutamate at ribbon synapses using time-lapse imaging, we identified two kinetically distinct release components: a rapid response that was exhausted within 50-100 ms and a slower and sustained response lasting the entire stimulation. After repeated stimulations, the recovery of the fast component followed a biphasic time course. Depression of glutamate release was largely responsible for the rapid firing rate adaptation recorded in the afferent neurons. However, postsynaptic Ca responses had a slower recovery time course compared to that of glutamate release, indicating that they are likely to contribute to the afferent firing adaptation. Hair cells also exhibited a form of adaptation during inhibitory bundle stimulations. We conclude that hair cells have optimised their synaptic machinery to encode prolonged stimuli and to maintain their sensitivity to new incoming stimuli.
本研究旨在确定活体中海马毛细胞带状突触的感觉适应特征。斑马鱼侧线的毛细胞将水动力刺激传递到后外侧线节神经元传入神经元。水射流刺激引起的兴奋性毛束偏转会导致谷氨酸在毛细胞突触释放，具有快速（相）和持续的成分，这可能与不同囊泡池的胞吐作用有关。传入神经元放电率随时间的适应，反映了神经递质释放的抑制，而不会阻止锁相。在抑制毛束位移期间也会发生适应，突出了在长时间刺激期间侧线敏感性范围的变化。突触后机制对传入神经元放电适应有一定程度的调节作用。我们的结论是，囊泡耗竭是放电率适应的主要决定因素，使侧线毛细胞带状突触能够保持对持续刺激的敏感性。
适应是感觉系统用来调整其对环境刺激的敏感性的一种手段，以适应环境刺激的变化。在听觉和前庭系统中，毛细胞带状突触中含谷氨酸的囊泡的释放特性在感觉适应中起着至关重要的作用，从而塑造了对持续刺激的神经反应。带状突触如何调节谷氨酸的释放以及它们如何在活体中调节传入反应在很大程度上仍然未知。在这里，我们使用双光子成像和电生理学技术在活体斑马鱼中研究了感觉适应背景下毛细胞的突触传递特征。毛细胞的立体纤毛束的长时间和重复水射刺激引起传入神经元中动作电位放电率的适应。通过使用时程成像监测带状突触处的谷氨酸，我们确定了两种动力学上不同的释放成分：快速反应，在 50-100 毫秒内耗尽，以及较慢和持续的反应，持续整个刺激过程。重复刺激后，快速成分的恢复遵循双相时间过程。谷氨酸释放的抑制在记录到的传入神经元中的快速放电率适应中起主要作用。然而，突触后 Ca 反应的恢复时间过程比谷氨酸释放的恢复时间过程慢，表明它们可能有助于传入神经元的放电适应。毛细胞在抑制束刺激期间也表现出一种适应形式。我们的结论是，毛细胞优化了它们的突触机制，以编码持续刺激并保持对新传入刺激的敏感性。
