Synapsin Determines Memory Strength after Punishment- and Relief-Learning
Synapsin Determines Memory Strength after Punishment- and Relief-Learning
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DOI：
10.1523/jneurosci.4454-14.2015
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发表时间：
2015-05-13
影响因子：
5.3
通讯作者：
Gerber, Bertram
中科院分区：
文献类型：
--
作者：
Niewalda, Thomas;Michels, Birgit;Gerber, Bertram
不良生活事件可以诱发两种具有相反效价的记忆，依赖于时间：对之前刺激的“负面”记忆和对“缓解”时刻经历的刺激的“正面”记忆。这种惩罚记忆和缓解记忆存在于昆虫、大鼠和人类中。例如，果蝇（Drosophila melanogaster）在气味休克训练（气味的“前向条件反射”）后避开气味，而在气味休克训练（气味的“后向条件反射”）后它们接近气味。这些依赖于时间的关联过程有共同的分子决定因素吗？我们专注于突触蛋白的作用，一个保守的突触前磷蛋白调节储备池和突触囊泡容易释放池之间的平衡。我们发现，缺乏突触蛋白会使与任务相关的感觉和运动能力不受影响。相比之下，惩罚记忆和缓解记忆的分数都降低了。这些缺陷反映了关联记忆强度的真正减弱，因为非关联处理中的失真（例如，对处理的敏感性、适应性、习惯性、致敏性）、辨别能力和符合检测的时间过程的变化可以被排除作为替代解释。在RNAi介导的突触蛋白敲低后，也观察到惩罚和释放记忆强度的降低，并且通过急性恢复突触蛋白和在突变果蝇的蘑菇体中局部恢复突触蛋白来拯救。因此，惩罚记忆和缓解记忆都需要突触蛋白，并且在这个意义上共享遗传和分子决定因素。我们注意到，人类惩罚记忆和缓解记忆之间的相应分子共性将限制选择性干扰过度联想惩罚记忆的药理学尝试，例如，在创伤经历之后。
Adverse life events can induce two kinds of memory with opposite valence, dependent on timing: "negative" memories for stimuli preceding them and "positive" memories for stimuli experienced at themoment of "relief." Such punishment memory and relief memory are found in insects, rats, and man. For example, fruit flies (Drosophila melanogaster) avoid an odor after odor-shock training ("forward conditioning" of the odor), whereas after shock odor training ("backward conditioning" of the odor) they approach it. Do these timing-dependent associative processes share molecular determinants? We focus on the role of Synapsin, a conserved presynaptic phosphoprotein regulating the balance between the reserve pool and the readily releasable pool of synaptic vesicles. We find that a lack of Synapsin leaves task-relevant sensory and motor faculties unaffected. In contrast, both punishment memory and relief-memory scores are reduced. These defects reflect a true lessening of associative memory strength, as distortions in nonassociative processing (e.g., susceptibility to handling, adaptation, habituation, sensitization), discrimination ability, and changes in the time course of coincidence detection can be ruled out as alternative explanations. Reductions in punishment- and relief-memory strength are also observed upon an RNAi-mediated knock-down of Synapsin, and are rescued both by acutely restoring Synapsin and by locally restoring it in the mushroom bodies of mutant flies. Thus, both punishment memory and relief memory require the Synapsin protein and in this sense share genetic and molecular determinants. We note that corresponding molecular commonalities between punishment memory and relief memory in humans would constrain pharmacological attempts to selectively interfere with excessive associative punishment memories, e.g., after traumatic experiences.