Dopamine-dependent effects on basal and glutamate stimulated network dynamics in cultured hippocampal neurons.

Dopamine-dependent effects on basal and glutamate stimulated network dynamics in cultured hippocampal neurons.
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DOI:
10.1111/jnc.13915
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发表时间:
2017-03
影响因子:
4.7
通讯作者:
Conant K
Conant K
中科院分区:
医学2区
文献类型:
--
作者:
Li Y;Chen X;Dzakpasu R;Conant K

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振荡活动发生在皮层和海马网络中,具有特定的频率范围,被认为对工作记忆、注意力、神经元前体的分化和记忆痕迹重放至关重要。相对较大的神经元群体内的同步活动受到单个细胞内的放电和爆发频率的影响,后者受到内在膜兴奋性和突触传递变化的调制。已发表的研究表明,多巴胺(DA),一种有效的学习和记忆调节剂,作用于多巴胺受体1样多巴胺受体(D1 R),影响谷氨酸受体亚单位的磷酸化和运输,沿着纹状体和前额叶皮层兴奋性突触传递的长时程增强(LTP)。先前的研究还表明,多巴胺可以影响这些区域的电压门控离子通道功能和膜兴奋性。很少有研究考察多巴胺对海马体中相关终点的影响,或网络爆发动力学方面的潜在后果。在本研究中,我们使用微电极阵列系统记录动作电位活动,以研究多巴胺在体外培养的小鼠海马神经元网络中调节基线和谷氨酸刺激的爆发活动的能力。我们发现,多巴胺刺激D1R依赖的增加,在其应用程序的几分钟内的整体爆发的数量。然而,值得注意的是,在本文使用的浓度下,多巴胺没有增加电极之间的脉冲串的总体同步性。虽然40分钟后爆发的次数恢复正常,但多巴胺预处理增强了对随后谷氨酸激发的反应。当同时给予两种调节剂时,未观察到谷氨酸刺激的爆发的多巴胺依赖性增强。与此同时,用多巴胺预处理小鼠海马培养物刺激谷氨酸受体亚基GluA1在丝氨酸845处磷酸化的持续增加。这种效果是一致的可能性,增强膜插入的GluAs可能有助于更缓慢地演变多巴胺依赖性增强谷氨酸刺激的爆发。总之,这些结果是一致的可能性,多巴胺可以影响海马爆发至少有两个时间上不同的机制,有助于新兴的赞赏多巴胺依赖的影响网络活动在海马。在这个问题上,我们表明多巴胺可以刺激神经网络活动的短期增加。多巴胺还可以增强网络活动,以响应后来的谷氨酸盐挑战。这些发现可能与奖励相关的增强记忆有关。
Oscillatory activity occurs in cortical and hippocampal networks with specific frequency ranges thought to be critical to working memory, attention, differentiation of neuronal precursors, and memory trace replay. Synchronized activity within relatively large neuronal populations is influenced by firing and bursting frequency within individual cells, and the latter is modulated by changes in intrinsic membrane excitability and synaptic transmission. Published work suggests that dopamine (DA), a potent modulator of learning and memory, acts on dopamine receptor 1-like dopamine receptors (D1Rs) to influence the phosphorylation and trafficking of glutamate receptor subunits, along with long-term potentiation (LTP) of excitatory synaptic transmission in striatum and prefrontal cortex. Prior studies also suggest that dopamine can influence voltage gated ion channel function and membrane excitability in these regions. Fewer studies have examined dopamine’s effect on related endpoints in hippocampus, or potential consequences in terms of network burst dynamics. In the present study, we record action potential activity using a micro-electrode array system to examine the ability of dopamine to modulate baseline and glutamate-stimulated bursting activity in an in vitro network of cultured murine hippocampal neurons. We show that dopamine stimulates a D1R-dependent increase in number of overall bursts within minutes of its application. Notably, however, at the concentration used herein, dopamine did not increase the overall synchrony of bursts between electrodes. Although the number of bursts normalizes by 40 minutes, bursting in response to a subsequent glutamate challenge is enhanced by dopamine pretreatment. Dopamine-dependent potentiation of glutamate-stimulated bursting was not observed when the two modulators were administered concurrently. In parallel, pretreatment of murine hippocampal cultures with dopamine stimulated lasting increases in the phosphorylation of the glutamate receptor subunit GluA1 at serine 845. This effect is consistent with the possibility that enhanced membrane insertion of GluAs may contribute to a more slowly evolving dopamine-dependent potentiation of glutamate-stimulated bursting. Together, these results are consistent with the possibility that dopamine can influence hippocampal bursting by at least two temporally distinct mechanisms, contributing to an emerging appreciation of dopamine-dependent effects on network activity in the hippocampus. In this issue we show that dopamine can stimulate a short-term increase in neuronal network activity. Dopamine can also potentiate increased network activity in response to a later glutamate challenge. These findings may be of relevance to enhanced memory that is associated with reward.
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期刊: NATURE PROTOCOLS
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