Adenosine A1 receptor antagonist-induced facilitation of postsynaptic AMPA currents in pyramidal neurons of the rat hippocampal CA2 area
Adenosine A1 receptor antagonist-induced facilitation of postsynaptic AMPA currents in pyramidal neurons of the rat hippocampal CA2 area
复制标题
腺苷 A1 受体拮抗剂诱导大鼠海马 CA2 区锥体神经元突触后 AMPA 电流的促进
DOI：
10.1007/s11302-022-09897-9
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发表时间：
2022
影响因子：
3.5
通讯作者：
Sekino Yuko
中科院分区：
文献类型：
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作者：
Kawamura Masahito;Sekino Yuko
腺苷 A1 受体 (A1R) 广泛表达于海马锥体神经元及其突触前末梢。众所周知，内源性腺苷通过激活海马锥体神经元中的 A1R 来调节海马功能，并且有报道称，阻断 A1R 会诱导 CA2 锥体神经元比 CA1 锥体神经元更强的兴奋性突触传递增强。 CA2 神经元的这种强烈增强被认为是由突触后 A1R 兴奋性突触传递的特异性调节引起的。然而，由于成熟海马 CA2 神经元膜片钳记录的技术困难，A1R 对突触后 AMPA 通道的直接影响仍不清楚。我们记录了 CA1 和 CA2 锥体神经元的突触电流，并分析了 A1R 拮抗剂对刺激诱发的突触传递和局部应用诱发的突触后 AMPA 电流的影响。拮抗剂增加了 CA1 和 CA2 神经元诱发突触传递的幅度。 CA2 锥体神经元中的这种促进作用比 CA1 中更大。该拮抗剂还增加了 CA2 神经元的突触后 AMPA 电流，但不增加 CA1 神经元的突触后 AMPA 电流。这种 CA2 AMPA 电流的促进作用被细胞内 G 蛋白阻断剂的应用所阻断。即使阻断了突触后 G 蛋白信号传导，A1R 拮抗剂仍会增加 CA2 神经元中诱发的突触传递。这些结果表明 CA2 锥体神经元的突触传递受到突触前和突触后 A1R 的调节。此外，A1R 通过 AMPA 电流的特征性突触后调节来调节 CA2 锥体神经元的兴奋性突触传递。
Adenosine A1receptors (A1R) are widely expressed in hippocampal pyramidal neurons and their presynaptic terminals. It is well known that endogenous adenosine regulates hippocampal function through the activation of A1R in hippocampal pyramidal neurons and has been reported that blockade of A1R induces stronger potentiation of excitatory synaptic transmission in CA2 pyramidal neurons than in CA1 pyramidal neurons. This strong potentiation of CA2 neurons is thought to be caused by the specific modulation of excitatory synaptic transmission through postsynaptic A1R. However, the direct effects of A1R on postsynaptic AMPA channels remain unknown because of the technical difficulties of patch-clamp recording from mature hippocampal CA2 neurons. We recorded synaptic currents from pyramidal neurons in CA1 and CA2 and analyzed the effects of an A1R antagonist on stimulation-evoked synaptic transmission and local application-induced postsynaptic AMPA currents. The antagonist increased the amplitude of evoked synaptic transmission in neurons in both CA1 and CA2. This facilitation was larger in pyramidal neurons in CA2 than in CA1. The antagonist also increased postsynaptic AMPA currents in neurons in CA2 but not in CA1. This facilitation of CA2 AMPA currents was occluded by the intracellular application of a G-protein blocker. Even with the blockade of postsynaptic G-protein signaling, the A1R antagonist increased evoked synaptic transmission in neurons in CA2. These results suggest that synaptic transmission in pyramidal neurons in CA2 is regulated by both presynaptic and postsynaptic A1R. Moreover, A1R regulate excitatory synaptic transmission in pyramidal neurons in CA2 through the characteristic postsynaptic modulation of AMPA currents.