Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
HiLife Neuroscience Center, University of Helsinki, Helsinki, Finland.
Mol Brain. 2023 May 20;16(1):43. doi: 10.1186/s13041-023-01035-9.
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.
红藻氨酸型谷氨酸受体 (KARs) 在 GABA 能中间神经元中表达丰富，并通过离子型和 G 蛋白偶联机制调节其功能。GABA 能中间神经元对于新生儿和成年大脑中协调的网络活动的产生至关重要，但中间神经元 KAR 在网络同步中的作用尚不清楚。在这里，我们表明，选择性缺乏 GABA 能神经元中的 GluK1 KAR 的新生小鼠海马中的 GABA 能神经传递和自发性网络活动受到干扰。中间神经元 GluK1 KAR 的内源性活性维持自发新生儿网络爆发的频率和持续时间，并通过海马网络抑制其传播。在成年雄性小鼠中，GABA 能神经元中缺乏 GluK1 导致更强的海马γ振荡和增强的θ-γ交叉频率耦合，同时在 Barnes 迷宫中的空间再学习更快。在雌性中，中间神经元 GluK1 的缺失导致短的尖峰涟漪振荡和灵活排序任务的能力略有受损。此外，中间神经元 GluK1 的消融导致一般活动和新物体回避减少，而仅引起轻微的焦虑表型。这些数据表明，GluK1 包含的 KAR 在 GABA 能中间神经元中在调节不同发育阶段海马体中的生理网络动力学方面起着关键作用。
