AMPA receptor modulators have different impact on hippocampal pyramidal cells and interneurons.
AMPA receptor modulators have different impact on hippocampal pyramidal cells and interneurons.
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AMPA受体调节剂对海马锥体细胞和中间神经元有不同的影响。
DOI：
10.1016/j.neuroscience.2005.06.031
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Arai,AC
中科院分区：
文献类型：
--
作者：
Xia,Y-F;Arai,AC
AMPA受体的正向调节剂增强突触的可塑性和记忆编码。AMPA受体电流的易化不仅导致兴奋性神经元的激活增强，而且通过上调兴奋性输入来增加抑制性中间神经元的活性。然而，除了锥体神经元外，人们对这些调节剂对细胞的影响以及它们对局部微电路的影响知之甚少。本研究观察了三个亚家族调节剂(主要是CX516、CX546和环硫氮化物)对四类海马CA1区神经元兴奋性突触反应以及兴奋性和双突触诱导的抑制场电位的影响。本实验观察了锥体细胞、位于放射层和东方的两种抑制性中间神经元以及新型兴奋性神经元放射层巨细胞对兴奋性突触后电流的影响。加入CX516后，锥体细胞EPSC波幅的增加是中间神经元的2~3倍，是放射状巨细胞的6倍。CX546对反应持续时间的影响同样在锥体细胞中最大。然而，这种药物在东方层和放射状中间神经元之间也有很强的分化，后者的增幅是后者的四倍。相反，环噻嗪对所有细胞类型的反应持续时间都有相似的影响。在现场记录中，CX516增强兴奋性突触后电位(EPSP)的能力是反馈或前馈电路的几倍，因为它对锥体细胞的影响更大。相反，CX546类似物BDP-20在增强前馈抑制方面比EPSPS或反馈抑制更有效。这种对前馈电路的偏爱可能与其在放射层比东方中间神经元具有更高的潜能有关。总而言之，AMPA受体调节剂在主要类型的神经元中的效力和/或有效性有很大的不同，这可能会对它们对电路和行为的影响产生影响。
Positive modulators of AMPA receptors enhance synaptic plasticity and memory encoding. Facilitation of AMPA receptor currents not only results in enhanced activation of excitatory neurons but also increases the activity of inhibitory interneurons by up-modulating their excitatory input. However, little is known about the effects of these modulators on cells other than pyramidal neurons and about their impact on local microcircuits. This study examined the effects of members from three subfamilies of modulators (mainly CX516, CX546 and cyclothiazide) on excitatory synaptic responses in four classes of hippocampal CA1 neurons and on excitatory and disynaptically induced inhibitory field potentials in hippocampal slices. Effects on excitatory postsynaptic currents (EPSCs) were examined in pyramidal cells, in two types of inhibitory interneurons located in stratum radiatum and oriens, and in stratum radiatum giant cells, a novel type of excitatory neuron. With CX516, increases in EPSC amplitude in pyramidal cells were two to three times larger than in interneurons and six times larger than in radiatum giant cells. The effects of CX546 on response duration similarly were largest in pyramidal cells. However, this drug also strongly differentiated between stratum oriens and radiatum interneurons with increases being four times larger in the latter. In contrast, cyclothiazide had similar effects on response duration in all cell types. In field recordings, CX516 was several times more potent in enhancing excitatory postsynaptic potentials (EPSPs) than feedback or feedforward circuits, as expected from its larger influence on pyramidal cells. In contrast, BDP-20, a CX546 analog, was more potent in enhancing feedforward inhibition than either EPSPs or feedback inhibition. This preference for feedforward over feedback circuits is probably related to its higher potency in stratum radiatum versus oriens interneurons. Taken together, AMPA receptor modulators differ substantially in their potency and/or efficacy across major classes of neurons which is likely to have consequences with regard to their impact on circuits and behavior.