Fiacco Todd A, McCarthy Ken D
Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7365, USA.
J Neurosci. 2004 Jan 21;24(3):722-32. doi: 10.1523/JNEUROSCI.2859-03.2004.
Spontaneous neurotransmitter release and activation of group I metabotropic glutamate receptors (mGluRs) each play a role in the plasticity of neuronal synapses. Astrocytes may contribute to short- and long-term synaptic changes by signaling to neurons via these processes. Spontaneous whole-cell AMPA receptor (AMPAR) currents were recorded in CA1 pyramidal cells in situ while evoking Ca2+ increases in the adjacent stratum radiatum astrocytes by uncaging IP3. Whole-cell patch clamp was used to deliver caged IP3 and the Ca2+ indicator dye Oregon green BAPTA-1 to astrocytes. Neurons were patch-clamped and filled with Alexa 568 hydrazide dye to visualize their morphological relationship to the astrocyte. On uncaging of IP3, astrocyte Ca2+ responses reliably propagated as a wave into the very fine distal processes, synchronizing Ca2+ activity within astrocyte microdomains. The intracellular astrocyte Ca2+ wave coincided with a significant increase in the frequency of AMPA spontaneous EPSCs, but with no change in their kinetics. AMPAR current amplitudes were increased as well, but not significantly (p = 0.06). The increased frequency of AMPAR currents was sensitive to the group I mGluR antagonists LY367385 and 2-methyl-6-(phenylethynyl)-pyridine, suggesting that (1) astrocytes released glutamate in response to IP3 uncaging, and (2) glutamate released by astrocytes activated group I mGluRs to facilitate the release of glutamate from excitatory neuronal presynaptic boutons. These results extend previous studies, which have shown astrocyte modulation of neuronal activity in vitro and suggest that astrocyte-to-neuron signaling in intact tissue may contribute to synaptic plasticity.
自发性神经递质释放和I组代谢型谷氨酸受体（mGluRs）的激活在神经元突触可塑性中均发挥作用。星形胶质细胞可能通过这些过程向神经元发出信号，从而促成短期和长期的突触变化。在原位CA1锥体细胞中记录自发性全细胞AMPA受体（AMPAR）电流，同时通过释放IP3在相邻的辐射层星形胶质细胞中引发Ca2+增加。采用全细胞膜片钳技术将笼锁IP3和Ca2+指示剂染料 Oregon green BAPTA-1递送至星形胶质细胞。对神经元进行膜片钳记录，并填充Alexa 568酰肼染料以观察其与星形胶质细胞的形态关系。释放IP3后，星形胶质细胞的Ca2+反应可靠地以波的形式传播到非常细小的远端突起中，使星形胶质细胞微区内的Ca2+活性同步。细胞内星形胶质细胞Ca2+波与AMPA自发性兴奋性突触后电流（EPSCs）频率的显著增加同时出现，但动力学无变化。AMPAR电流幅度也有所增加，但不显著（p = 0.06）。AMPAR电流频率的增加对I组mGluR拮抗剂LY367385和2-甲基-6-（苯乙炔基）-吡啶敏感，这表明：（1）星形胶质细胞对IP3释放做出反应而释放谷氨酸；（2）星形胶质细胞释放的谷氨酸激活I组mGluRs，以促进兴奋性神经元突触前终扣释放谷氨酸。这些结果扩展了先前的研究，先前研究已表明星形胶质细胞在体外对神经元活动的调节作用，并提示完整组织中星形胶质细胞与神经元之间的信号传递可能有助于突触可塑性。
