Wang Yang, Wang Zhan, Wang Jiangang, Wang Yali, Henderson Zaineb, Wang Xiaofang, Zhang Xi, Song Jinggui, Lu Chengbiao
Key Laboratory for the Brain Research of Henan Province, Xinxiang Medical University, Henan Province, Henan PR. China.
Institute of Membrane and System Biology, University of Leeds, Leeds, England.
Sci Rep. 2015 Mar 26;5:9493. doi: 10.1038/srep09493.
γ oscillations are associated with higher brain functions such as memory, perception and consciousness. Disruption of γ oscillations occur in various neuro-psychological disorders such as schizophrenia. Nicotinic acetylcholine receptors (nAChR) are highly expressed in the hippocampus, however, little is known about the role on hippocampal persistent γ oscillation. This study examined the effects of nicotine and selective nAChR agonists and antagonists on kainate-induced persistent γ oscillation in rat hippocampal slices. Nicotine enhanced γ oscillation at concentrations of 0.1-10 μM, but reduced it at a higher concentration of 100 μM. The enhancement on γ oscillation can be best mimicked by co-application of α4β2- and α7-nAChR agonist and reduced by a combination of nAChR antagonists, DhβE and MLA. However, these nAChR antagonists failed to block the suppressing role of nicotine on γ. Furthermore, we found that the NMDA receptor antagonist D-AP5 completely blocked the effect of nicotine. These results demonstrate that nicotine modulates γ oscillations via α7 and α4β2 nAChR as well as NMDA activation, suggesting that nAChR activation may have a therapeutic role for the clinical disorder such as schizophrenia, which is known to have impaired γ oscillation and hypo-NMDA receptor function.
γ振荡与记忆、感知和意识等高级脑功能相关。γ振荡的破坏发生在多种神经心理障碍中，如精神分裂症。烟碱型乙酰胆碱受体（nAChR）在海马体中高度表达，然而，其对海马体持续性γ振荡的作用却知之甚少。本研究考察了尼古丁以及选择性nAChR激动剂和拮抗剂对大鼠海马体切片中由红藻氨酸诱导的持续性γ振荡的影响。尼古丁在0.1 - 10 μM浓度下增强γ振荡，但在100 μM的较高浓度下则使其减弱。联合应用α4β2 - 和α7 - nAChR激动剂能最佳模拟对γ振荡的增强作用，而nAChR拮抗剂DhβE和MLA的组合则使其减弱。然而，这些nAChR拮抗剂未能阻断尼古丁对γ振荡的抑制作用。此外，我们发现NMDA受体拮抗剂D - AP5完全阻断了尼古丁的作用。这些结果表明，尼古丁通过α7和α4β2 nAChR以及NMDA激活来调节γ振荡，这表明nAChR激活可能对精神分裂症等临床疾病具有治疗作用，已知这些疾病存在γ振荡受损和NMDA受体功能低下的情况。
