Genetic evidence for the requirement of adenylyl cyclase 1 in synaptic scaling of forebrain cortical neurons
Genetic evidence for the requirement of adenylyl cyclase 1 in synaptic scaling of forebrain cortical neurons
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DOI：
10.1111/j.1460-9568.2007.05669.x
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发表时间：
2007-07-01
影响因子：
3.4
通讯作者：
Zhuo, Min
中科院分区：
文献类型：
--
作者：
Gong, Bo;Wang, Hansen;Zhuo, Min
稳态可塑性对于稳定神经元回路的活动水平很重要。神经元稳态可塑性响应活动剥夺的分子机制尚不完全清楚。我们发现，6-氰基-7-硝基喹喔啉-2,3-二酮（CNQX）长时间阻断α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体会导致培养的前脑皮层神经元中更大、更快的微型兴奋性突触后电流（mEPSC）事件，频率增加。此外，GluR1 蛋白水平和 CREB 依赖性转录上调。阻断 L 型 Ca2+ 通道（但不阻断红藻氨酸受体）产生与阻断 AMPA 受体相似的效果。 AC1（腺苷酸环化酶 1）的基因缺失，而非关键神经元腺苷酸环化酶 AC8，可显着减少不活动引起的 GluR1 变化。我们的结果表明同聚 GluR1 AMPA 受体的合成以及由于皮质中的突触不活动而可能插入到突触中。 AC1 通过将 L 型 Ca2+ 通道的信号耦合到下游信号通路，在此过程中发挥亚型选择性作用。
Homeostatic plasticity is important to stabilize the activity level of neuronal circuits. Molecular mechanisms underlying neuronal homeostatic plasticity in response to activity deprivation are not completely understood. We found that prolonged alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor blockade by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) resulted in larger, faster miniature excitatory postsynaptic current (mEPSC) events with enhanced frequency in cultured forebrain cortical neurons. Furthermore, GluR1 protein level and CREB-dependent transcription were up-regulated. Blockade of L-type Ca2+ channels but not kainate receptors produced similar effects to the AMPA receptor blockade. Genetic deletion of AC1 (adenylyl cyclase 1), but not AC8, a key neuronal adenylyl cyclase, significantly reduced inactivity-induced GluR1 changes. Our results indicate the synthesis of homomeric GluR1 AMPA receptors and their possible insertion into synapses due to synaptic inactivity in the cortex. AC1 plays a subtype selective role in this process by coupling signals from L-type Ca2+ channels to downstream signalling pathways.