Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Eur J Neurosci. 2013 Apr;37(8):1242-7. doi: 10.1111/ejn.12125. Epub 2013 Jan 22.
Cortical networks display persistent activity in the form of periods of sustained synchronous depolarizations ('UP states') punctuated by periods of relative hyperpolarization ('DOWN states'), which together form the slow oscillation. UP states are known to be synaptically generated and are sustained by a dynamic balance of excitation and inhibition, with fast ionotropic glutamatergic excitatory and GABAergic inhibitory conductances increasing during the UP state. Previously, work from our group demonstrated that slow metabotropic GABA receptors also play an important role in terminating the UP state, but the effects of other neuromodulators on this network phenomenon have received little attention. Given that persistent activity is a neural correlate of working memory and that signalling through dopamine receptors has been shown to be critical for working memory tasks, we examined whether dopaminergic neurotransmission affected the slow oscillation. Here, using an in vitro model of the slow oscillation in rat medial entorhinal cortex, we showed that dopamine strongly and reversibly suppressed cortical UP states. We showed that this effect was mediated through D1 -like and not D2 -like dopamine receptors, and we found no evidence that tonic dopaminergic transmission affected UP states in our model.
皮质网络以持续同步去极化的形式表现出持久的活动（“UP 状态”），被相对超极化的时期（“DOWN 状态”）打断，这两者共同构成了慢波振荡。已知 UP 状态是由突触产生的，并由兴奋和抑制的动态平衡维持，在 UP 状态期间快速离子型谷氨酸能兴奋性和 GABA 能抑制性电导增加。先前，我们小组的工作表明，慢代谢型 GABA 受体也在终止 UP 状态中发挥重要作用，但其他神经调质对这种网络现象的影响却很少受到关注。鉴于持续活动是工作记忆的神经相关物，并且多巴胺受体的信号传递已被证明对工作记忆任务至关重要，我们研究了多巴胺能神经传递是否会影响慢波振荡。在这里，我们使用大鼠内侧隔核的慢波振荡体外模型表明，多巴胺强烈且可逆地抑制了皮质 UP 状态。我们表明，这种作用是通过 D1 样而不是 D2 样多巴胺受体介导的，并且我们在我们的模型中没有发现证据表明紧张性多巴胺能传递会影响 UP 状态。
