Pain Research Center, Department of Anesthesiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267, USA.
Pain Research Center, Department of Anesthesiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267, USA.
Neurosci Lett. 2021 Apr 17;750:135794. doi: 10.1016/j.neulet.2021.135794. Epub 2021 Mar 2.
A subset of glutamatergic interneurons in the neonatal spinal superficial dorsal horn (SDH) exhibits intrinsic burst-firing (i.e. 'pacemaker' activity), which is tightly regulated by persistent, voltage-gated Na channels and classic inward-rectifying K (K2) channels and downregulated over the course of postnatal development. Ascending lamina I projection neurons targeting the parabrachial nucleus (PB) or periaqueductal gray (PAG) can also display pacemaker activity during early life. However, the degree to which the ionic mechanisms driving pacemaker activity are conserved across different cell types in the spinal dorsal horn, as well as whether the intrinsic bursting is restricted to newborn projection neurons, remains to be elucidated. Using in vitro patch clamp recordings from identified lamina I spinoparabrachial neurons in rat spinal cord slices, here we demonstrate that adolescent projection neurons retain their ability to generate pacemaker activity. In contrast to previous findings in lamina I interneurons, pacemaker projection neurons possessed higher membrane capacitance, lower membrane resistance, and a greater K-mediated conductance compared to adjacent spinoparabrachial neurons that lacked intrinsic burst-firing. Nonetheless, as previously seen in interneurons, the bath application of riluzole to block persistent Na channels significantly dampened pacemaker activity in projection neurons. Collectively, these results suggest that intrinsic burst-firing in the developing dorsal horn can be generated by multiple combinations of ionic conductances, and highlight the need for further investigation into the mechanisms governing pacemaker activity within the major output neurons of the SDH network.
新生儿脊髓浅层背角（SDH）中的一组谷氨酸能中间神经元表现出固有爆发式（即“起搏器”活动），这种活动受到持续的电压门控 Na 通道和经典内向整流 K（K2）通道的严格调节，并在出生后发育过程中下调。靶向臂旁核（PB）或中脑导水管周围灰质（PAG）的升序 I 层投射神经元在生命早期也可以显示起搏器活动。然而，驱动起搏器活动的离子机制在脊髓背角中不同类型的细胞中是否保守，以及内在爆发是否仅限于新生投射神经元，仍有待阐明。在这里，我们使用大鼠脊髓切片中鉴定的 I 层脊髓-臂旁神经元的体外膜片钳记录，证明青春期投射神经元保留了产生起搏器活动的能力。与以前在 I 层中间神经元中发现的情况相反，与缺乏内在爆发的相邻脊髓-臂旁神经元相比，起搏器投射神经元具有更高的膜电容、更低的膜电阻和更大的 K 介导的电导。尽管如此，正如以前在中间神经元中看到的，用利鲁唑浴灌流阻断持续的 Na 通道显著抑制了投射神经元的起搏器活动。总之，这些结果表明，发育中的背角中的内在爆发式活动可以由多种离子电导的组合产生，并强调需要进一步研究 SDH 网络的主要输出神经元中起搏器活动的调节机制。
