Diabetes-, stress- and ageing-related changes in synaptic plasticity in hippocampus and neocortex - The same metaplastic process?
Diabetes-, stress- and ageing-related changes in synaptic plasticity in hippocampus and neocortex - The same metaplastic process?
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DOI：
10.1016/j.ejphar.2007.11.084
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发表时间：
2008-05-06
影响因子：
5
通讯作者：
Artola, Alain
中科院分区：
文献类型：
--
作者：
Artola, Alain
大脑中的学习和记忆可能通过突触传递中的活动依赖性、持久性变化而发生。迄今为止，已经确定了两种相反的活动依赖性突触修饰，即长时程增强和长时程抑制。在包括海马CA1和新皮质在内的许多脑区，突触后去极化的水平控制着可塑性的大小和标志：低去极化后获得长时程抑制，而长时程增强需要更强的去极化。突触可塑性也取决于先前的突触活动。突触可塑性的后续诱导的活动依赖性调节，称为“启动”或“后可塑性”，至少部分是由于引发突触可塑性所需的突触后去极化水平的伴随相反变化：在先前激活或增强的突触中，与幼稚突触相比，长时程增强的诱导需要更大的去极化，而长时程抑制的诱导需要更小的去极化。即增强被抑制而抑制被促进，在抑制的突触中反之亦然。包括人类在内的许多物种在衰老、疾病（糖尿病等）和心理侮辱（压力，.）。有趣的是，糖尿病，压力和老年大鼠显示出强大的长时程抑郁和长时程增强。但是，在元可塑性，诱导长时程增强需要一个更大的突触后去极化和长期抑郁症的一个较小的年轻对照组动物相比。此外，糖尿病和活动依赖性调制的突触可塑性表现出闭塞。这表明糖尿病、压力和衰老通过与元可塑性相同的机制作用于突触可塑性。这种长时程增强的持续抑制和长时程抑制的易化可能导致活动依赖性突触减弱并导致认知障碍。(C)2008 Elsevier B.V.保留所有权利。
Learning and memory in the brain likely occur through activity-dependent, long-lasting changes in synaptic transmission. Two opposite activity-dependent synaptic modifications have been identified so far, long-term potentiation and long-term depression. In many brain areas including hippocampal CA1 and neocortex, the level of postsynaptic depolarization controls the magnitude and sign of plasticity: long-term depression is obtained after low depolarizations, whereas long-term potentiation requires stronger ones. Synaptic plasticity also depends on prior synaptic activity. Activity-dependent modulation of subsequent induction of synaptic plasticity, termed "priming" or "metaplasticity", is due, at least in part, to concomitant opposite shifts in the levels of postsynaptic depolarization needed to elicit synaptic plasticity: in previously activated or potentiated synapses, induction of long-term potentiation requires a larger depolarization and that of long-term depression a smaller one compared with naive synapses - i.e. potentiation is inhibited and depression promoted - and vice versa in depressed synapses. Many species including humans express cognitive deficits during ageing, diseases (diabetes mellitus, ...) and psychological insults (stress, ...). Interestingly, diabetic, stressed and aged rats show robust long-term depression and long-term potentiation. But, as in metaplasticity, induction of long-term potentiation requires a larger postsynaptic depolarization and that of long-term depression a smaller one compared with young control animals. Moreover, diabetes- and activity-dependent modulation of synaptic plasticity exhibit occlusion. This suggests that diabetes, stress and ageing act on synaptic plasticity through common mechanisms with metaplasticity. Such persistent inhibition of long-term potentiation and facilitation of long-term depression might lead to activity-dependent synapse weakening and contribute to cognitive impairments. (C) 2008 Elsevier B.V. All rights reserved.