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在活体动态钳位研究中观察小鼠下丘脑中的 I(h)。

In vivo dynamic clamp study of I(h) in the mouse inferior colliculus.

机构信息

Department of Neuroscience, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

出版信息

J Neurophysiol. 2010 Aug;104(2):940-8. doi: 10.1152/jn.00264.2010. Epub 2010 Jun 10.

DOI:10.1152/jn.00264.2010
PMID:20538776
Abstract

Approximately half of the cells in the mouse inferior colliculus have the hyperpolarization-activated mixed cation current I(h), yet little is known about its functional relevance in vivo. We therefore studied its contribution to the processing of sound information in single cells by making in vivo whole cell recordings from the inferior colliculus (IC) of young-adult anesthetized C57Bl/6 mice. Following pharmacological block of the endogenous channels, a dynamic clamp approach allowed us to study the responses to current injections or auditory stimuli in the presence and absence of I(h) within the same neuron, thus avoiding network or developmental effects. The presence of I(h) changed basic cellular properties, including depolarizing the resting membrane potential and decreasing resting membrane resistance. Sound-evoked excitatory postsynaptic potentials were smaller but at the same time reached a more positive membrane potential when I(h) was present. With I(h), a subset of cells showed rebound spiking following hyperpolarizing current injection. Its presence also changed more complex cellular properties. It decreased temporal summation in response to both hyperpolarizing and depolarizing repetitive current stimuli, and resulted in small changes in the cycle-averaged membrane potential during sinusoidal amplitude modulated (SAM) tones. Furthermore, I(h) minimally decreased the response to a tone following a depolarization, an effect that may make a small contribution to forward masking. Our results thus suggest that previously observed differences in IC cells are a mixture of direct effects of I(h) and indirect effects due to the change in membrane potential or effects due to the co-expression with other channels.

摘要

大约一半的小鼠下丘脑中的细胞具有超极化激活混合阳离子电流 I(h),但对于其在体内的功能相关性知之甚少。因此,我们通过对麻醉的 C57Bl/6 成年小鼠的下丘脑中进行体内全细胞膜片钳记录,研究了其对单个细胞中声音信息处理的贡献。在药理学阻断内源性通道后,动态钳位方法使我们能够在同一神经元中研究存在和不存在 I(h)时对电流注入或听觉刺激的反应,从而避免了网络或发育效应的影响。I(h) 的存在改变了基本的细胞特性,包括使静息膜电位去极化和降低静息膜电阻。当存在 I(h) 时,声音诱发的兴奋性突触后电位变小,但同时达到更正的膜电位。存在 I(h) 时,一组细胞在去极化电流注入后会出现反弹式放电。它的存在也改变了更复杂的细胞特性。它减少了对去极化和去极化重复电流刺激的时间总和,并且在正弦幅度调制 (SAM) 音调期间导致周期平均膜电位的微小变化。此外,I(h) 最小化了在去极化后对音调的反应,这种效应可能对前向掩蔽有微小贡献。因此,我们的研究结果表明,先前在下丘脑中观察到的细胞差异是 I(h)的直接影响和由于膜电位变化引起的间接影响以及由于与其他通道共同表达引起的影响的混合。

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