Activity-Dependent Bidirectional Regulation of GAD Expression in a Homeostatic Fashion Is Mediated by BDNF-Dependent and Independent Pathways.
Activity-Dependent Bidirectional Regulation of GAD Expression in a Homeostatic Fashion Is Mediated by BDNF-Dependent and Independent Pathways.
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DOI：
10.1371/journal.pone.0134296
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Iijima T
中科院分区：
文献类型：
--
作者：
Hanno-Iijima Y;Tanaka M;Iijima T
稳态突触可塑性或突触缩放是一种调节神经元传递以补偿神经元活动中长时间过度变化的机制。兴奋性和抑制性神经元都经历基于突触传递强度的稳态变化，这可以有效地有助于电路活动的微调。然而，GABA能（GABA，γ-氨基丁酸）神经元内稳态突触可塑性的基因调控仍然知之甚少。本研究证明了活动依赖性的动态缩放，其中NMDA-R（N-甲基-D-天冬氨酸受体）活性调节GABA合成酶：谷氨酸脱羧酶65和67（GAD 65和GAD 67）的表达。结果表明，活性调节的BDNF（脑源性神经营养因子）的释放是必要的，但不是足够的，这些GAD亚型的活性依赖性放大。活性依赖性GAD表达的双向形式需要BDNF依赖性和BDNF非依赖性途径，两者都由NMDA-R活性触发。另外的结果表明，这两个GAD基因不同的慢性变化的神经元活动，这可能部分是由差异依赖BDNF的反应。与GAD表达的活性依赖性双向缩放平行，本研究进一步观察到神经元活性的慢性变化导致GABA能神经元以稳态双向方式释放神经递质的改变。因此，GAD 65和67在神经元活动的长期变化过程中的差异表达可能与成熟GABA能突触前体的双向稳态可塑性的某些方面有关。
Homeostatic synaptic plasticity, or synaptic scaling, is a mechanism that tunes neuronal transmission to compensate for prolonged, excessive changes in neuronal activity. Both excitatory and inhibitory neurons undergo homeostatic changes based on synaptic transmission strength, which could effectively contribute to a fine-tuning of circuit activity. However, gene regulation that underlies homeostatic synaptic plasticity in GABAergic (GABA, gamma aminobutyric) neurons is still poorly understood. The present study demonstrated activity-dependent dynamic scaling in which NMDA-R (N-methyl-D-aspartic acid receptor) activity regulated the expression of GABA synthetic enzymes: glutamic acid decarboxylase 65 and 67 (GAD65 and GAD67). Results revealed that activity-regulated BDNF (brain-derived neurotrophic factor) release is necessary, but not sufficient, for activity-dependent up-scaling of these GAD isoforms. Bidirectional forms of activity-dependent GAD expression require both BDNF-dependent and BDNF-independent pathways, both triggered by NMDA-R activity. Additional results indicated that these two GAD genes differ in their responsiveness to chronic changes in neuronal activity, which could be partially caused by differential dependence on BDNF. In parallel to activity-dependent bidirectional scaling in GAD expression, the present study further observed that a chronic change in neuronal activity leads to an alteration in neurotransmitter release from GABAergic neurons in a homeostatic, bidirectional fashion. Therefore, the differential expression of GAD65 and 67 during prolonged changes in neuronal activity may be implicated in some aspects of bidirectional homeostatic plasticity within mature GABAergic presynapses.