Huxter John R, Zinyuk Larissa E, Roloff Eva v L, Clarke Vernon R J, Dolman Nigel P, More Julia C A, Jane David E, Collingridge Graham L, Muller Robert U
Department of Anatomy, Medical Research Council Centre for Synaptic Plasticity, University of Bristol, Bristol BS8 1TD, United Kingdom.
J Neurosci. 2007 Feb 28;27(9):2212-23. doi: 10.1523/JNEUROSCI.3954-06.2007.
We investigated the role of kainate receptors in the generation of theta oscillations using (S)-1-(2-amino-2-carboxyethyl)-3-(2-carboxythiophene-3-yl-methyl)pyrimidine-2,4-dione (UBP304), a novel, potent and highly selective antagonist of GLU(K5)-containing kainate receptors. EEG and single-unit recordings were made from the dorsal hippocampus of awake, freely moving rats trained to forage for food. Bilateral intracerebroventricular injections of UBP304 (2.0 microl, two times; 2.08 mM) caused a clear (approximately 25%) reduction in theta frequency that was dissociable from behavioral effects of the drug. The locations of firing fields of principal cells in the hippocampal formation were generally preserved, but both field firing rates and the precision of field organization decreased. UBP304 lowered the frequency of the theta modulation of hippocampal interneuron discharge, accurately matching the reduced frequency of the theta field oscillation. UBP308 [(R)-1-(2-amino-2-carboxyethyl)-3-(2-carboxythiophene-3-yl-methyl)pyrimidine-2,4-dione], the inactive enantiomer of UBP304, caused none of these effects. Our results suggest that GLU(K5) receptors have an important role in modulating theta activity. In addition, the effects on cellular responses provide both insight into the mechanisms of theta pacing, and useful information for models of temporal coding.
我们使用(S)-1-(2-氨基-2-羧乙基)-3-(2-羧基噻吩-3-基甲基)嘧啶-2,4-二酮(UBP304)，一种新型、强效且高度选择性的含GLU(K5)的红藻氨酸受体拮抗剂，研究了红藻氨酸受体在θ振荡产生中的作用。对经过觅食训练的清醒、自由活动大鼠的背侧海马进行脑电图和单单位记录。双侧脑室内注射UBP304(2.0微升，两次；2.08毫摩尔)导致θ频率明显降低(约25%)，这与该药物的行为效应无关。海马结构中主细胞放电场的位置通常得以保留，但场放电率和场组织的精确性均降低。UBP304降低了海马中间神经元放电的θ调制频率，与θ场振荡频率的降低精确匹配。UBP308[(R)-1-(2-氨基-2-羧乙基)-3-(2-羧基噻吩-3-基甲基)嘧啶-2,4-二酮]，UBP304的无活性对映体，未产生这些效应。我们的结果表明，GLU(K5)受体在调节θ活动中起重要作用。此外，对细胞反应的影响既有助于深入了解θ起搏机制，也为时间编码模型提供了有用信息。
