Metaplasticity of mossy fiber synaptic transmission involves altered release probability
Metaplasticity of mossy fiber synaptic transmission involves altered release probability
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DOI：
10.1523/jneurosci.20-09-03434.2000
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发表时间：
2000-05-01
影响因子：
5.3
通讯作者：
Beck, H
中科院分区：
文献类型：
--
作者：
Goussakov, IV;Fink, K;Beck, H
活动依赖性突触可塑性是中枢神经系统突触的基本特征。有趣的是，突触表达可塑性变化的能力本身受到相当大的活动依赖性变异或化塑性的影响。这些形式的高阶可塑性很重要，因为它们对于将突触维持在动态功能范围内可能至关重要。在这项研究中，我们探究了应用红藻氨酸诱导的体内神经元活动是否可以引起苔藓纤维短期和长期可塑性的持久变化。红藻氨酸诱导癫痫持续状态几周后，苔藓纤维（而不是联合连合通路）表现出配对脉冲促进、增强和长时程增强（LTP）的显着丧失。由于腺苷酸环化酶-蛋白激酶 A 级联参与苔藓纤维 LTP 诱导，因此我们通过腺苷酸环化酶或蛋白激酶 A 的药理激活测试了该关键途径的完整性。这些治疗导致对照动物出现 LTP，但红藻氨酸治疗的动物则不然，表明状态诱导的变化发生在蛋白激酶 A 的下游。为了测试神经递质释放的改变是否可能解释这些变化，我们测量了长满青苔的光纤终端。我们发现，红藻氨酸处理的大鼠中谷氨酸释放池的大小显着增加，表明苔藓纤维-CA3突触的释放概率增加。因此，我们认为，神经元活动引起的神经递质释放概率的持久变化可能是化塑性的强大机制，可调节癫痫持续状态后苔藓纤维-CA3突触的短期和长期可塑性。
Activity-dependent synaptic plasticity is a fundamental feature of CNS synapses. Intriguingly, the capacity of synapses to express plastic changes is itself subject to considerable activity-dependent variation, or metaplasticity. These forms of higher order plasticity are important because they may be crucial to maintain synapses within a dynamic functional range. In this study, we asked whether neuronal activity induced in vivo by application of kainate can induce lasting changes in mossy fiber short- and long-term plasticity.Several weeks after kainate-induced status epilepticus, the mossy fiber, but not the associational-commissural pathway, exhibits a marked loss of paired-pulse facilitation, augmentation, and long-term potentiation (LTP). Because the adenylyl cyclase-protein kinase A cascade is involved in mossy fiber LTP induction, we have tested the integrity of this key pathway by pharmacological activation of either adenylyl cyclase or protein kinase A. These treatments resulted in LTP in control, but not in kainate-treated animals, indicating that status-induced changes occur downstream of protein kinase A. To test whether altered neurotransmitter release might account for these changes, we measured the size of the releasable pool of glutamate in mossy fiber terminals. We find that the size of the releasable pool of glutamate was significantly increased in kainate-treated rats, indicating an increased release probability at the mossy fiber-CA3 synapse.Therefore, we suggest that lasting changes in neurotransmitter release probability caused by neuronal activity may be a powerful mechanism for metaplasticity that modulates both short- and long-term plasticity in the mossy fiber-CA3 synapse after status epilepticus.