Department of Mathematics and Statistics, University of Exeter, Exeter EX4 4QF, United Kingdom.
Biorobotics Laboratory, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
J Neurosci. 2023 Feb 22;43(8):1387-1404. doi: 10.1523/JNEUROSCI.0520-22.2022. Epub 2023 Jan 24.
Developing spinal circuits generate patterned motor outputs while many neurons with high membrane resistances are still maturing. In the spinal cord of hatchling frog tadpoles of unknown sex, we found that the firing reliability in swimming of inhibitory interneurons with commissural and ipsilateral ascending axons was negatively correlated with their cellular membrane resistance. Further analyses showed that neurons with higher resistances had outward rectifying properties, low firing thresholds, and little delay in firing evoked by current injections. Input synaptic currents these neurons received during swimming, either compound, unitary current amplitudes, or unitary synaptic current numbers, were scaled with their membrane resistances, but their own synaptic outputs were correlated with membrane resistances of their postsynaptic partners. Analyses of neuronal dendritic and axonal lengths and their activities in swimming and cellular input resistances did not reveal a clear correlation pattern. Incorporating these electrical and synaptic properties into a computer swimming model produced robust swimming rhythms, whereas randomizing input synaptic strengths led to the breakdown of swimming rhythms, coupled with less synchronized spiking in the inhibitory interneurons. We conclude that the recruitment of these developing interneurons in swimming can be predicted by cellular input resistances, but the order is opposite to the motor-strength-based recruitment scheme depicted by Henneman's size principle. This form of recruitment/integration order in development before the emergence of refined motor control is progressive potentially with neuronal acquisition of mature electrical and synaptic properties, among which the scaling of input synaptic strengths with cellular input resistance plays a critical role. The mechanisms on how interneurons are recruited to participate in circuit function in developing neuronal systems are rarely investigated. In 2d-old frog tadpole spinal cord, we found the recruitment of inhibitory interneurons in swimming is inversely correlated with cellular input resistances, opposite to the motor-strength-based recruitment order depicted by Henneman's size principle. Further analyses showed the amplitude of synaptic inputs that neurons received during swimming was inversely correlated with cellular input resistances. Randomizing/reversing the relation between input synaptic strengths and membrane resistances in modeling broke down swimming rhythms. Therefore, the recruitment or integration of these interneurons is conditional on the acquisition of several electrical and synaptic properties including the scaling of input synaptic strengths with cellular input resistances.
在许多具有高膜电阻的神经元仍在成熟的过程中,发育中的脊髓回路会产生模式化的运动输出。在性别未知的孵化期蛙幼体的脊髓中,我们发现具有连合和同侧上升轴突的抑制性中间神经元在游泳中的放电可靠性与它们的细胞膜电阻呈负相关。进一步的分析表明,电阻较高的神经元具有外向整流特性、较低的放电阈值,并且在电流注入时放电延迟很小。这些神经元在游泳过程中接收的输入突触电流,无论是复合电流幅度、单位电流幅度还是单位突触电流数量,都与它们的膜电阻成比例,但它们自身的突触输出与它们的突触后伙伴的膜电阻相关。在游泳过程中,神经元树突和轴突的长度及其活动和细胞输入电阻的分析没有揭示出清晰的相关模式。将这些电和突触特性纳入计算机游泳模型中,产生了稳健的游泳节律,而随机化输入突触强度则导致游泳节律的崩溃,同时抑制性中间神经元的放电也变得不同步。我们得出结论,这些发育中的中间神经元在游泳中的募集可以通过细胞输入电阻来预测,但顺序与亨纳曼大小原则所描述的基于运动强度的募集方案相反。在出现精细运动控制之前,这种发育中的募集/整合顺序是渐进的,可能伴随着神经元获得成熟的电和突触特性,其中输入突触强度与细胞输入电阻的比例起着关键作用。在发育中的神经元系统中,中间神经元如何被募集参与回路功能的机制很少被研究。在 2 日龄的蛙幼体脊髓中,我们发现游泳中的抑制性中间神经元的募集与细胞输入电阻呈负相关,与亨纳曼大小原则所描述的基于运动强度的募集顺序相反。进一步的分析表明,神经元在游泳过程中接收的突触输入幅度与细胞输入电阻呈负相关。在建模中随机化/反转输入突触强度和膜电阻之间的关系会破坏游泳节律。因此,这些中间神经元的募集或整合是有条件的,取决于它们获得包括输入突触强度与细胞输入电阻的比例在内的几种电和突触特性。