Department of Laboratory, The Second Xiangya Hospital, Central South University, Changsha 410011, China.
Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha 410013, China.
Neuropharmacology. 2014 Feb;77:277-84. doi: 10.1016/j.neuropharm.2013.10.004. Epub 2013 Oct 20.
Oxytocin (OT) was reported to affect cognitive and emotional behavior by action in ventral tegmental area (VTA) and other brain areas. However, it is still unclear how OT activates VTA and related midline nucleus. Here, using patch-clamp recording, we studied the effects of OT on neuron activity in VTA and interfascicular nucleus (IF). OT dose-dependently and selectively excited small neurons located in medial VTA and the majority of IF neurons but not large neurons in lateral VTA. We found the hyperpolarization-activated current (I(h)) and the membrane capacitance of OT-sensitive neuron were significantly smaller than those of OT-insensitive neurons. The action potential width of OT-sensitive neurons was about half that of OT-insensitive neurons. The OT effect was blocked by the OT receptor antagonist atosiban and WAY-267464 but not by tetrodotoxin, suggesting a direct postsynaptic activation of OT receptors. In addition, the phospholipase C (PLC) inhibitor U73122 antagonized the depolarization by OT. Both the nonselective cation channel (NSCC) antagonist SKF96365 and the Na(+)-Ca(2+) exchanger (NCX) blocker SN-6 attenuated OT effects. These results suggested that the PLC signaling pathway coupling to NSCC and NCX contributes to the OT-mediated activation of neurons in medial VTA and IF. Taken together, our results indicate OT directly acted on medial VTA and especially IF neurons to activate NSCC and NCX via PLC. The direct activation by OT of midbrain neurons may be one mechanism underlying OT effects on social behavior.
催产素（OT）被报道通过作用于腹侧被盖区（VTA）和其他脑区来影响认知和情绪行为。然而，OT 如何激活 VTA 及其相关中线核仍然不清楚。在这里，我们使用膜片钳记录研究了 OT 对 VTA 和束间核（IF）神经元活动的影响。OT 剂量依赖性和选择性地兴奋位于 VTA 内侧和大多数 IF 神经元但不兴奋 VTA 外侧大神经元的小神经元。我们发现 OT 敏感神经元的超极化激活电流（I（h））和膜电容明显小于 OT 不敏感神经元。OT 敏感神经元的动作电位宽度约为 OT 不敏感神经元的一半。OT 效应被 OT 受体拮抗剂阿托西班和 WAY-267464 阻断，但被河豚毒素不阻断，表明 OT 受体的直接突触后激活。此外，PLC 抑制剂 U73122 拮抗 OT 引起的去极化。非选择性阳离子通道（NSCC）拮抗剂 SKF96365 和 Na（+）-Ca（2+）交换体（NCX）阻滞剂 SN-6 均减弱 OT 作用。这些结果表明，PLC 信号通路与 NSCC 和 NCX 偶联，有助于 OT 介导的 VTA 内侧和 IF 神经元的激活。总之，我们的结果表明 OT 直接作用于 VTA 内侧，特别是 IF 神经元，通过 PLC 激活 NSCC 和 NCX。OT 对中脑神经元的直接激活可能是 OT 对社会行为影响的一种机制。
