Iigaya Kamon, Onimaru Hiroshi, Ikeda Keiko, Iizuka Makito, Izumizaki Masahiko
Department of Physiology, Showa University School of Medicine, Tokyo, 142-8555, Japan.
Department of Oral Physiology, Showa University School of Dentistry, Tokyo, 142-8555, Japan.
Pflugers Arch. 2025 Jan;477(1):131-145. doi: 10.1007/s00424-024-03031-x. Epub 2024 Oct 14.
The ventromedial hypothalamus (VMH) plays an important role in feeding behavior and control of the sympathetic nervous system (SNS). The VMH includes a group of neurons that exhibit strong synchronized rhythmic burst firing (so-called VMH oscillation). This VMH oscillation is glucose inhibited, responsive to feeding-related peptides, and is functionally coupled to outputs of the SNS. However, the details of its rhythm generation and synchronization mechanisms are unknown. In the present study, we investigated cellular mechanisms of VMH oscillation by means of electrophysiological recordings and calcium imaging in juvenile rat slice preparations including the VMH. In the electrophysiological study, we performed membrane potential recording from neurons in the vicinity of pipettes for field potential recording. We found that the rhythmic bursts in the VMH were preserved in low Ca/high Mg synaptic transmission blockade solution. During membrane hyperpolarization by current injection, the action potential was largely inhibited, but fluctuation of the membrane potential remained with a frequency similar to that at resting potential level. The electric VMH oscillation disappeared after application of either a gap junction blocker, carbenoxolone (100 µM), or a persistent sodium channel blocker, riluzole (20 µM). Membrane potentials and input resistances of rhythmic burst neurons in the VMH were not significantly changed during these manipulations. A calcium imaging study revealed that all VMH cells exhibiting synchronized rhythmic activity detected by intracellular calcium increases were silenced following the application of carbenoxolone. These results suggest that VMH oscillation arises from the activation of persistent sodium channels and coupling via gap junctions.
腹内侧下丘脑（VMH）在进食行为和交感神经系统（SNS）控制中发挥重要作用。VMH包含一组表现出强烈同步节律性爆发式放电的神经元（即所谓的VMH振荡）。这种VMH振荡受葡萄糖抑制，对进食相关肽有反应，并且在功能上与SNS的输出相耦合。然而，其节律产生和同步机制的细节尚不清楚。在本研究中，我们通过在包含VMH的幼年大鼠脑片标本中进行电生理记录和钙成像，研究了VMH振荡的细胞机制。在电生理研究中，我们从用于场电位记录的移液管附近的神经元进行膜电位记录。我们发现，在低钙/高镁突触传递阻断溶液中，VMH中的节律性爆发得以保留。在通过电流注入使膜超极化期间，动作电位受到很大抑制，但膜电位的波动仍然存在，其频率与静息电位水平时相似。在应用缝隙连接阻断剂卡本氧肟酸（100 μM）或持续性钠通道阻断剂利鲁唑（20 μM）后，电VMH振荡消失。在这些操作过程中，VMH中有节律性爆发的神经元的膜电位和输入电阻没有显著变化。一项钙成像研究表明，在应用卡本氧肟酸后，所有通过细胞内钙增加检测到的表现出同步节律活动的VMH细胞均沉默。这些结果表明，VMH振荡源于持续性钠通道的激活以及通过缝隙连接的耦合。
