PDF(Pubmed)
Abstract：
Kainate type glutamate receptors (KARs) are strongly expressed in GABAergic interneurons and have the capability of modulating their functions via ionotropic and G-protein coupled mechanisms. GABAergic interneurons are critical for generation of coordinated network activity in both neonatal and adult brain, yet the role of interneuronal KARs in network synchronization remains unclear. Here, we show that GABAergic neurotransmission and spontaneous network activity is perturbed in the hippocampus of neonatal mice lacking GluK1 KARs selectively in GABAergic neurons. Endogenous activity of interneuronal GluK1 KARs maintains the frequency and duration of spontaneous neonatal network bursts and restrains their propagation through the hippocampal network. In adult male mice, the absence of GluK1 in GABAergic neurons led to stronger hippocampal gamma oscillations and enhanced theta-gamma cross frequency coupling, coinciding with faster spatial relearning in the Barnes maze. In females, loss of interneuronal GluK1 resulted in shorter sharp wave ripple oscillations and slightly impaired abilities in flexible sequencing task. In addition, ablation of interneuronal GluK1 resulted in lower general activity and novel object avoidance, while causing only minor anxiety phenotype. These data indicate a critical role for GluK1 containing KARs in GABAergic interneurons in regulation of physiological network dynamics in the hippocampus at different stages of development.
摘要：
红藻酸盐型谷氨酸受体（KARs）在GABA能中间神经元中强烈表达，并具有通过离子型和G蛋白偶联机制调节其功能的能力。GABA能中间神经元对于新生儿和成人大脑协调网络活动的产生至关重要。然而,神经元间KAR在网络同步中的作用尚不清楚.这里,我们表明，在GABA能神经元中选择性缺乏GluK1KARs的新生小鼠的海马中，GABA能神经传递和自发网络活动受到干扰。神经元间GluK1KARs的内源性活动维持自发性新生儿网络爆发的频率和持续时间，并抑制其通过海马网络的传播。在成年雄性小鼠中，GABA能神经元中GluK1的缺失导致更强的海马伽马振荡和增强的theta-gamma交叉频率耦合，与巴恩斯迷宫中更快的空间再学习相吻合。在女性中，神经元间GluK1的丢失导致较短的尖锐波纹波振荡，并在灵活的测序任务中略微受损。此外,间神经元GluK1的消融导致较低的一般活动和新的对象回避，而只引起轻微的焦虑表型。这些数据表明，在不同发育阶段，GABA能中间神经元中含有GluK1的KAR在调节海马生理网络动力学中的关键作用。
