Role of the neurogranin concentrated in spines in the induction of long-term potentiation
Role of the neurogranin concentrated in spines in the induction of long-term potentiation
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DOI：
10.1523/jneurosci.0729-06.2006
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发表时间：
2006-07-12
影响因子：
5.3
通讯作者：
Lisman, John E.
中科院分区：
文献类型：
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作者：
Zhabotinsky, Anatol M.;Camp, R. Nicholas;Lisman, John E.
CA 1海马神经元的突触可塑性依赖于Ca 2+升高和由此产生的钙调素依赖性酶的激活。长时程抑制（LTD）的诱导依赖于钙调磷酸酶，而长时程增强（LTP）依赖于Ca 2 +/钙调蛋白依赖性蛋白激酶II（caMKII）。神经元中钙调素的浓度远低于脱钙钙调素结合蛋白神经颗粒蛋白和GAP-43的总浓度，导致静息状态下游离钙调素的水平较低。神经颗粒蛋白高度集中在树突棘中。为了阐明神经颗粒蛋白在突触可塑性中的作用，我们构建了一个计算模型，重点是钙调素与神经颗粒蛋白，钙调神经磷酸酶和CaMKII的相互作用。该模型显示了LTD或LTP诱导过程中发生的Ca 2+瞬变如何影响钙调蛋白，以及由此产生的钙调磷酸酶和CaMKII的激活如何影响AMPA受体介导的传递。在该模型中，敲除神经颗粒素强烈地减少了由单个100 Hz，1 s强直引起的LTP，并略微增强LTD，与实验数据雅阁。我们的模拟表明，钙调素之间的交流棘和它的父母树突是有限的。因此，诱导LTP与短破伤风需要钙调蛋白储存在棘的形式迅速解离钙调蛋白-神经颗粒蛋白复合物。
Synaptic plasticity in CA1 hippocampal neurons depends on Ca2+ elevation and the resulting activation of calmodulin-dependent enzymes. Induction of long-term depression (LTD) depends on calcineurin, whereas long-term potentiation (LTP) depends on Ca2+/calmodulin-dependent protein kinase II (caMKII). The concentration of calmodulin in neurons is considerably less than the total concentration of the apocalmodulin-binding proteins neurogranin and GAP-43, resulting in a low level of free calmodulin in the resting state. Neurogranin is highly concentrated in dendritic spines. To elucidate the role of neurogranin in synaptic plasticity, we constructed a computational model with emphasis on the interaction of calmodulin with neurogranin, calcineurin, and CaMKII. The model shows how the Ca2+ transients that occur during LTD or LTP induction affect calmodulin and how the resulting activation of calcineurin and CaMKII affects AMPA receptor-mediated transmission. In the model, knockout of neurogranin strongly diminishes the LTP induced by a single 100 Hz, 1 s tetanus and slightly enhances LTD, in accord with experimental data. Our simulations show that exchange of calmodulin between a spine and its parent dendrite is limited. Therefore, inducing LTP with a short tetanus requires calmodulin stored in spines in the form of rapidly dissociating calmodulin-neurogranin complexes.