Homolog of protein kinase Mζ maintains context aversive memory and underlying long-term facilitation in terrestrial snail Helix
Homolog of protein kinase Mζ maintains context aversive memory and underlying long-term facilitation in terrestrial snail Helix
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DOI：
10.3389/fncel.2015.00222
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发表时间：
2015-06-22
影响因子：
5.3
通讯作者：
Malyshev, Aleksey Y.
中科院分区：
文献类型：
--
作者：
Balaban, Pavel M.;Roshchin, Matvey;Malyshev, Aleksey Y.
研究表明，在大脑的不同区域和不同物种中，多种长期记忆会被一种持续活跃的蛋白激酶M - zeta （PKM - zeta）的局部抑制迅速抹去。利用哺乳动物PKM zeta抗体，我们在本研究中描述了陆蜗牛螺旋lucorum神经系统中免疫反应分子的定位。转录组学证实了PKM zeta同源物的存在。我们在行为实验中证明，在PKM zeta选择性肽阻断剂zeta抑制肽（ZIP）阻断PKM zeta时，情境恐惧记忆消失，而在打乱ZIP的情况下，情境恐惧记忆消失。如果ZIP与提醒（有害情境下20分钟）结合使用，则未观察到长期情境记忆的损害。在电生理实验中，我们研究了PKM zeta是否参与神经回路中长期促进（LTF）的维持。高频神经刺激联合5 -羟色胺浴可诱导运动前中间神经元兴奋性突触输入的LTF，持续时间至少为4小时。我们发现，在破伤风后第90分钟，2 × 10-6 M ZIP浴可使EPSP振幅降至未破伤风的EPSP值。在相同的时间和浓度下应用错开的ZIP肽对EPSP振幅没有影响。为了测试ZIP的作用是否对突触具有特异性，我们进行了局部谷氨酸应用对体膜反应的LTF实验。早期研究表明，在这种人工突触条件下应用血清素会引起对谷氨酸的LTF反应。我们发现ZIP在这些条件下对LTF没有影响，这可能是由于免疫化学证明这些鉴定的神经元体细胞中PKM zeta分子的浓度很低。这些结果表明PKM zeta的Helix同源物可能参与了地蜗牛神经系统诱导后长期变化的维持。
It has been shown that a variety of long-term memories in different regions of the brain and in different species are quickly erased by local inhibition of protein kinase M zeta (PKM zeta), a persistently active protein kinase. Using antibodies to mammalian PKM zeta, we describe in the present study the localization of immunoreactive molecules in the nervous system of the terrestrial snail Helix lucorum. Presence of a homolog of PKM zeta was confirmed with transcriptomics. We have demonstrated in behavioral experiments that contextual fear memory disappeared under a blockade of PKM zeta with a selective peptide blocker of PKM zeta zeta inhibitory peptide (ZIP), but not with scrambled ZIP. If ZIP was combined with a reminder (20 min in noxious context), no impairment of the long-term contextual memory was observed. In electrophysiological experiments we investigated whether PKM zeta takes part in the maintenance of long-term facilitation (LTF) in the neural circuit mediating tentacle withdrawal. LTF of excitatory synaptic inputs to premotor interneurons was induced by high-frequency nerve stimulation combined with serotonin bath applications and lasted at least 4 h. We found that bath application of 2 x 10-6 M ZIP at the 90th min after the tetanization reduced the EPSP amplitude to the non-tetanized EPSP values. Applications of the scrambled ZIP peptide at a similar time and concentration didnt affect the EPSP amplitudes. In order to test whether effects of ZIP are specific to the synapses, we performed experiments with LTF of somatic membrane responses to local glutamate applications. It was shown earlier that serotonin application in such an artificial synapse condition elicits LTF of responses to glutamate. It was found that ZIP had no effect on LTF in these conditions, which may be explained by the very low concentration of PKM zeta molecules in somata of these identified neurons, as evidenced by immunochemistry. Obtained results suggest that the Helix homolog of PKM zeta might be involved in postinduction maintenance of long-term changes in the nervous system of the terrestrial snail.