Weiss Torsten, Veh Rüdiger W, Heinemann Uwe
Institute of Anatomy, University Hospital Charité, Humboldt-University Berlin, Philippstr. 12, D-10115 Berlin, Germany.
Eur J Neurosci. 2003 Nov;18(9):2573-80. doi: 10.1046/j.1460-9568.2003.02970.x.
The dopaminergic neuronal system is implicated in cognitive processes in a variety of brain regions including the mesolimbic system. We have investigated whether dopamine also affects synchronized network activity in the hippocampus, which has been ascribed to play a pivotal role in memory formation. Gamma frequency (20-80 Hz) oscillations were induced by the cholinergic agonist carbachol. Oscillatory activity was examined in area CA3 of Wistar rat hippocampal slices, employing field potential and intracellular recordings. Application of carbachol initiated synchronized population activity in the gamma band at 40 Hz. Induced gamma activity persisted over hours and required GABAA receptors. Dopamine reversibly decreased the integrated gamma band power of the carbachol rhythm by 62%, while its frequency was not changed. By contrast, individual pyramidal cells recorded during carbachol-induced field gamma activity exhibited theta frequency (5-15 Hz) membrane potential oscillations that were not altered by dopamine. The dopamine effect on the field gamma activity was mimicked by the D1 receptor agonist SKF-383393 and partially antagonized by the D1 antagonist SCH-23390. Conversely, the D2 receptor agonist quinpirole failed to depress the oscillations, and the D2 antagonist sulpiride did not prevent the suppressive dopamine effect. The data indicate that dopamine strongly depresses cholinergic gamma oscillations in area CA3 of rat hippocampus by activation of D1-like dopamine receptors and that this effect is most likely mediated via impairment of interneurons involved in generation and maintenance of the carbachol-induced network rhythm.
多巴胺能神经元系统与包括中脑边缘系统在内的多个脑区的认知过程有关。我们研究了多巴胺是否也会影响海马体中的同步网络活动，海马体在记忆形成中被认为起着关键作用。胆碱能激动剂卡巴胆碱可诱导γ频率（20 - 80赫兹）振荡。利用场电位和细胞内记录技术，在Wistar大鼠海马切片的CA3区检测振荡活动。应用卡巴胆碱可引发40赫兹γ波段的同步群体活动。诱导的γ活动可持续数小时，且需要GABAA受体。多巴胺可使卡巴胆碱节律的整合γ波段功率可逆性降低62%，但其频率不变。相比之下，在卡巴胆碱诱导的场γ活动期间记录的单个锥体细胞表现出θ频率（5 - 15赫兹）的膜电位振荡，且不受多巴胺影响。D1受体激动剂SKF - 383393可模拟多巴胺对场γ活动的作用，D1拮抗剂SCH - 23390可部分拮抗该作用。相反，D2受体激动剂喹吡罗未能抑制振荡，D2拮抗剂舒必利也不能阻止多巴胺的抑制作用。数据表明，多巴胺通过激活D1样多巴胺受体强烈抑制大鼠海马CA3区的胆碱能γ振荡，且这种作用很可能是通过损害参与卡巴胆碱诱导的网络节律产生和维持的中间神经元介导的。
