GABAB receptors modulate NMDA receptor calcium signals in dendritic spines.

GABAB receptors modulate NMDA receptor calcium signals in dendritic spines.
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DOI:
10.1016/j.neuron.2010.03.012
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发表时间:
2010-04-15
期刊:
影响因子:
16.2
通讯作者:
Carter AG
Carter AG
中科院分区:
医学1区
文献类型:
--
作者:
Chalifoux JR;Carter AG

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代谢性GABAB受体在调节整个大脑的神经元和电路的兴奋性中起着重要作用。这些受体通过抑制突触前释放或激活突触后钾通道来影响突触传递。然而,它们直接影响不同类型的突触后谷氨酸受体的能力仍未得到解决。本研究研究了小鼠前额皮质2/3层锥体神经元中GABAB受体的调节。我们使用双光子激光扫描显微镜来研究单个树突棘的突触调制。利用双光子光学量子分析,我们首次证明了单突触中多泡释放的强大突触前调制。通过双光子谷氨酸释放,我们发现GABAB受体强烈抑制NMDA受体钙信号。这种突触后调节通过PKA途径发生,不影响AMPA或NMDA受体介导的突触电流。这种新形式的GABAB受体调节对钙依赖性神经元功能的控制具有广泛的意义。
Metabotropic GABAB receptors play a fundamental role in modulating the excitability of neurons and circuits throughout the brain. These receptors influence synaptic transmission by inhibiting presynaptic release or activating postsynaptic potassium channels. However, their ability to directly influence different types of postsynaptic glutamate receptors remains unresolved. Here we examine GABAB receptor modulation in layer 2/3 pyramidal neurons from the mouse prefrontal cortex. We use two-photon laser-scanning microscopy to study synaptic modulation at individual dendritic spines. Using two-photon optical quantal analysis, we first demonstrate robust presynaptic modulation of multivesicular release at single synapses. Using two-photon glutamate uncaging, we then reveal that GABAB receptors strongly inhibit NMDA receptor calcium signals. This postsynaptic modulation occurs via the PKA pathway and does not affect synaptic currents mediated by AMPA or NMDA receptors. This novel form of GABAB receptor modulation has widespread implications for the control of calcium-dependent neuronal function.
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