Comparable GABAergic mechanisms of hippocampal seizurelike activity in posttetanic and low-Mg2+ conditions

Comparable GABAergic mechanisms of hippocampal seizurelike activity in posttetanic and low-Mg2+ conditions
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DOI:
10.1152/jn.00238.2005
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发表时间:
2006-03-01
影响因子:
2.5
通讯作者:
Takada, M
Takada, M
中科院分区:
医学3区
文献类型:
--
作者:
Fujiwara-Tsukamoto, Y;Isomura, Y;Takada, M

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已知GABA是成熟哺乳动物脑中的主要抑制性神经递质,但当突触后Cl-浓度变高时,该物质的作用有时转变为去极化甚至兴奋性。最近,我们已经表明,在正常细胞外液中由强直刺激诱导的强直样后放电(强直后后放电)是通过成熟海马CA 1区锥体细胞中的GABA能兴奋介导的。在这项研究中,我们研究了可能的贡献类似的去极化/兴奋性GABA能输入的CA 1锥体细胞在低细胞外Mg 2+条件下,另一个实验模型的癫痫发作活动(低Mg 2+后放电)诱导的类癫痫后放电。在大多数情况下,GABA(A)拮抗剂荷包牡丹碱灌注可消除低Mg ~(2+)后放电,但不能消除发作间期样活动。每个振荡反应在低Mg 2+后放电依赖于Cl-电导,并包含一个F-不敏感的去极化成分在锥体细胞,从而表明后放电反应可能是通过GABA能和nonGABA能传输介导的。此外,本地GABA应用程序记录的细胞显示,GABA反应确实是去极化过程中的低镁2 + afterdischarge。此外,GABA能中间神经元位于皮层和oriens的振荡周期比那些在其他层的CA 1区更活跃。这些结果表明,去极化GABA能输入可能促进振荡同步海马CA 1区锥体细胞之间的低Mg ~(2+)后放电的方式类似的表达强直后放电。
It is known that GABA is a major inhibitory neurotransmitter in mature mammalian brains, but the effect of this substance is sometimes converted into depolarizing or even excitatory when the postsynaptic Cl- concentration becomes high. Recently we have shown that seizurelike afterdischarge induced by tetanic stimulation in normal extracellular fluid (posttetanic afterdischarge) is mediated through GABAergic excitation in mature hippocampal CA1 pyramidal cells. In this study, we examined the possible contribution of similar depolarizing/excitatory GABAergic input to the CA1 pyramidal cells to the seizurelike afterdischarge induced in a low extracellular Mg2+ condition, another experimental model of epileptic seizure activity (low-Mg2+ afterdischarge). Perfusion of the GABA(A) antagonist bicuculline abolished the low-Mg2+ afterdischarge, but not the interictal-like activity, in most cases. Each oscillatory response during the low-Mg2+ afterdischarge was dependent on Cl- conductance and contained an F--insensitive depolarizing component in the pyramidal cells, thus indicating that the afterdischarge response may be mediated through both GABAergic and nonGABAergic transmissions. In addition, local GABA application to the recorded cells revealed that GABA responses were indeed depolarizing during the low-Mg2+ afterdischarge. Furthermore, the GABAergic interneurons located in the strata pyramidale and oriens fired in oscillatory cycles more actively than those in other layers of the CA1 region. These results suggest that the depolarizing GABAergic input may facilitate oscillatory synchronization among the hippocampal CA1 pyramidal cells during the low-Mg2+ afterdischarge in a manner similar to the expression of the posttetanic afterdischarge.