Institut für Physiologie I, Westfälische Wilhelms-Universität, 48149, Münster, Germany.
Davee Department of Neurology and Clinical Neurosciences and Department of Physiology, Feinberg School of Medicine, Northwestern University, 60611Chicago, USA.
Brain Struct Funct. 2018 Apr;223(3):1537-1564. doi: 10.1007/s00429-017-1559-z. Epub 2017 Nov 22.
Hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels have important functions in controlling neuronal excitability and generating rhythmic oscillatory activity. The role of tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) in regulation of hyperpolarization-activated inward current, I , in the thalamocortical system and its functional relevance for the physiological thalamocortical oscillations were investigated. A significant decrease in I current density, in both thalamocortical relay (TC) and cortical pyramidal neurons was found in TRIP8b-deficient mice (TRIP8b). In addition basal cAMP levels in the brain were found to be decreased while the availability of the fast transient A-type K current, I , in TC neurons was increased. These changes were associated with alterations in intrinsic properties and firing patterns of TC neurons, as well as intrathalamic and thalamocortical network oscillations, revealing a significant increase in slow oscillations in the delta frequency range (0.5-4 Hz) during episodes of active-wakefulness. In addition, absence of TRIP8b suppresses the normal desynchronization response of the EEG during the switch from slow-wave sleep to wakefulness. It is concluded that TRIP8b is necessary for the modulation of physiological thalamocortical oscillations due to its direct effect on HCN channel expression in thalamus and cortex and that mechanisms related to reduced cAMP signaling may contribute to the present findings.
超极化激活环核苷酸门控阳离子（HCN）通道在控制神经元兴奋性和产生节律性振荡活动方面具有重要功能。本研究旨在探讨四肽重复结构域 Rab8b 相互作用蛋白（TRIP8b）在调节丘脑皮质系统中的超极化激活内向电流（I）中的作用及其对生理丘脑皮质振荡的功能相关性。研究发现，TRIP8b 缺失小鼠（TRIP8b）中，I 电流密度在丘脑皮质中继（TC）和皮质锥体神经元中均显著降低。此外，大脑中的基础 cAMP 水平降低，而 TC 神经元中快速瞬态 A 型钾电流（I）的可利用性增加。这些变化与 TC 神经元的内在特性和放电模式以及丘脑内和丘脑皮质网络振荡的改变有关，表明在活跃觉醒期间，δ频带（0.5-4 Hz）的慢振荡明显增加。此外，TRIP8b 的缺失抑制了 EEG 在从慢波睡眠到觉醒的转换过程中的正常去同步反应。研究结果表明，由于 TRIP8b 直接影响丘脑和皮质中的 HCN 通道表达，因此它对于调节生理丘脑皮质振荡是必需的，而与降低 cAMP 信号转导相关的机制可能与本研究结果有关。
