Increased basal synaptic inhibition of hippocampal area CA1 pyramidal neurons by an antiepileptic drug that enhances I(H).
Increased basal synaptic inhibition of hippocampal area CA1 pyramidal neurons by an antiepileptic drug that enhances I(H).
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DOI：
10.1038/npp.2009.150
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发表时间：
2010-01
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影响因子：
--
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超极化激活的阳离子电流IH调节许多可兴奋细胞的电活动，但其精确功能因细胞类型而异。抗癫痫药物拉莫三嗪（LTG）最近被证明可以增强海马CA1锥体神经元的IH，揭示了一种潜在的抗惊厥机制，因为IH可以抑制这些细胞中兴奋性突触后电位的树突体传播。然而，IH也在许多海马中间神经元中表达，这些中间神经元向CA1锥体神经元提供突触抑制，因此，IH调节可以通过直接调节中间神经元活性来间接调节主细胞的抑制性控制。海马中间神经元中的IH是否对LTG的调制敏感，以及这可能如何影响锥体细胞的突触抑制尚未研究。在这项研究中，我们研究了LTG对IH和CA1区s.o.自发放电的影响。在未成熟大鼠脑切片中，对CA1锥体神经元中的自发抑制性突触后电流（sIPSC）的影响。LTG（100 µM）显著增加大多数中间神经元的IH，并使中间神经元从静息状态去极化，促进自发放电。LTG还引起锥体神经元中自发（但不是微型）IPSC的频率增加，而不显著改变振幅或上升和衰减时间。这些数据表明，IH在CA1中间神经元可以增加LTG，类似于IH在锥体神经元，IH增强增加中间神经元兴奋性，这些影响与增加的基础突触抑制CA1锥体神经元。
The hyperpolarization-activated cation current IH regulates the electrical activity of many excitable cells, but its precise function varies across cell types. The antiepileptic drug lamotrigine (LTG) recently was shown to enhance IH in hippocampal CA1 pyramidal neurons, revealing a potential anticonvulsant mechanism, as IH can dampen dendrito-somatic propagation of excitatory postsynaptic potentials in these cells. However, IH also is expressed in many hippocampal interneurons that provide synaptic inhibition to CA1 pyramidal neurons, and thus, IH modulation may indirectly regulate inhibitory control of principal cells via direct modulation of interneuron activity. Whether IH in hippocampal interneurons is sensitive to modulation by LTG, and how this may affect synaptic inhibition of pyramidal cells has not been investigated. In this study, we examined the effects of LTG on IH and spontaneous firing of area CA1 s.o. interneurons, and on spontaneous inhibitory postsynaptic currents (sIPSCs) in CA1 pyramidal neurons in immature rat brain slices. LTG (100 µM) significantly increased IH in the majority of interneurons, and depolarized interneurons from rest, promoting spontaneous firing. LTG also caused an increase in the frequency of spontaneous (but not miniature) IPSCs in pyramidal neurons without significantly altering amplitudes or rise and decay times. These data indicate that IH in CA1 interneurons can be increased by LTG, similarly to IH in pyramidal neurons, that IH enhancement increases interneuron excitability, and that these effects are associated with increased basal synaptic inhibition of CA1 pyramidal neurons.
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影响因子：
82.9
作者：
Chen, K;Baram, TZ;Soltesz, I
通讯作者：
Soltesz, I
影响因子：
5.5
作者：
Maccaferri, G;McBain, CJ
通讯作者：
McBain, CJ
影响因子：
2.5
作者：
Berger, T;Larkum, ME;Lüscher, HR
通讯作者：
Lüscher, HR
影响因子：
3.3
作者：
Bender, RA;Brewster, A;Baram, TZ
通讯作者：
Baram, TZ
DOI：
10.1016/s0169-328x(00)00155-8
发表时间：
2000-09-30
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Monteggia, LM;Eisch, AJ;Nestler, EJ
通讯作者：
Nestler, EJ