Henan International-Joint Laboratory for Non-invasive Neural Modulation/The Key Laboratory for the Brain Research of Henan Province, Department of Physiology, Xinxiang Medical University, Xinxiang 453003, China; The Second Hospital of Jinhua, Jinhua, Zhejiang 321000, China.
Henan International-Joint Laboratory for Non-invasive Neural Modulation/The Key Laboratory for the Brain Research of Henan Province, Department of Physiology, Xinxiang Medical University, Xinxiang 453003, China; Key Laboratory of Clinical Psychopharmacology, School of Pharmacy, Xinxiang Medical University, Xinxiang 453003, China.
Neuroscience. 2021 Nov 1;475:83-92. doi: 10.1016/j.neuroscience.2021.09.005. Epub 2021 Sep 14.
Network oscillations at γ frequency band (30-80 Hz), generated by the interaction between inhibitory interneurons and excitatory neurons, have been proposed to be associated with higher brain functions such as learning and memory. Dopamine (DA), one of the major CNS transmitters, modulates hippocampal γ oscillations but the intracellular mechanisms involved remain elusive. In this study, we recorded kainate-induced γ oscillations in the CA3 area of rat hippocampal slices, and found that DA strongly enhanced γ power, which was largely blocked by dopamine receptor 1 (DR1) antagonist SCH23390, receptor tyrosine kinase (RTK) inhibitor UNC569 and ERK inhibitor U0126, partially blocked by D2/3R antagonist raclopride, PKA inhibitor H89 and PI3K inhibitor wortmannin, but not affected by AKT inhibitor TCBN or NMDAR antagonist D-AP5. Our results indicate that DA-mediated γ enhancement is involved in the activation of signaling pathway of DR1/2-RTK-ERK. Our data demonstrate a strong, rapid modulation of DA on hippocampal γ oscillations and provide a new insight into cellular mechanisms of DA-mediated γ oscillations.
γ 频段（30-80Hz）的网络振荡是由抑制性中间神经元和兴奋性神经元相互作用产生的，被认为与学习和记忆等高级脑功能有关。多巴胺（DA）是中枢神经系统的主要递质之一，调节海马γ 振荡，但涉及的细胞内机制仍不清楚。在这项研究中，我们记录了大鼠海马切片 CA3 区的海人酸诱导的γ 振荡，发现 DA 强烈增强了γ 功率，这主要被多巴胺受体 1（DR1）拮抗剂 SCH23390、受体酪氨酸激酶（RTK）抑制剂 UNC569 和 ERK 抑制剂 U0126 阻断，部分被 D2/3R 拮抗剂氯丙嗪、PKA 抑制剂 H89 和 PI3K 抑制剂wortmannin 阻断，而 AKT 抑制剂 TCBN 或 NMDAR 拮抗剂 D-AP5 不影响。我们的结果表明，DA 介导的 γ 增强涉及 DR1/2-RTK-ERK 信号通路的激活。我们的数据表明，DA 对海马γ 振荡有强烈而快速的调制作用，并为 DA 介导的γ 振荡的细胞机制提供了新的见解。
