CAMKII REGULATES THE FREQUENCY-RESPONSE FUNCTION OF HIPPOCAMPAL SYNAPSES FOR THE PRODUCTION OF BOTH LTD AND LTP
CAMKII REGULATES THE FREQUENCY-RESPONSE FUNCTION OF HIPPOCAMPAL SYNAPSES FOR THE PRODUCTION OF BOTH LTD AND LTP
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DOI：
10.1016/0092-8674(95)90009-8
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发表时间：
1995-06-16
期刊：
影响因子：
64.5
通讯作者：
ODELL, TJ
中科院分区：
文献类型：
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作者：
MAYFORD, M;WANG, J;ODELL, TJ
为了研究突触可塑性中CaMKII的自磷酸化形式的功能，我们产生了表达一种激酶的转基因小鼠，该激酶是由于Thr-286点突变为天冬氨酸而非Ca 2+依赖性的，其模拟自磷酸化。表达突变形式的激酶的小鼠显示出增加的Ca 2+非依赖性CaMKII活性水平，类似于LTP后所见。然而，小鼠对100 Hz刺激的反应表现出正常的LTP。然而，在较低的频率下，在1-10 Hz的范围内，在转基因动物中产生的突触变化的大小和方向存在系统性的转变，有利于LTD。由Ca 2+非依赖性CaMKII活性对这种频率响应功能的调节似乎解释了两种以前无法解释的突触现象，与幼年动物相比，成年动物中LTD的相对损失以及抑制易化突触的能力增强。
To investigate the function of the autophosphorylated form of CaMKII in synaptic plasticity, we generated transgenic mice that express a kinase that is Ca2+ independent as a result of a point mutation of Thr-286 to aspartate, which mimics autophosphorylation. Mice expressing the mutant form of the kinase show an increased level of Ca2+-independent CaMKII activity similar to that seen following LTP. The mice nevertheless exhibit normal LTP in response to stimulation at 100 Hz. However, at lower frequencies, in the range of 1-10 Hz, there is a systematic shift in the size and direction of the resulting synaptic change in the transgenic animals that favors LTD. The regulation of this frequency-response function by Ca2+-independent CaMKII activity seems to account for two previously unexplained synaptic phenomena, the relative loss of LTD in adult animals compared with juveniles and the enhanced capability for depression of facilitated synapses.