Fuchs Elke C, Zivkovic Aleksandar R, Cunningham Mark O, Middleton Steven, Lebeau Fiona E N, Bannerman David M, Rozov Andrei, Whittington Miles A, Traub Roger D, Rawlins J Nicholas P, Monyer Hannah
Department of Clinical Neurobiology, University Hospital of Neurology, IZN, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany.
Neuron. 2007 Feb 15;53(4):591-604. doi: 10.1016/j.neuron.2007.01.031.
Perisomatic inhibition provided by a subgroup of GABAergic interneurons plays a critical role in timing the output of pyramidal cells. To test their contribution at the network and the behavioral level, we generated genetically modified mice in which the excitatory drive was selectively reduced either by the knockout of the GluR-D or by conditional ablation of the GluR-A subunit in parvalbumin-positive cells. Comparable cell type-specific reductions of AMPA-mediated currents were obtained. Kainate-induced gamma oscillations exhibited reduced power in hippocampal slices from GluR-D-/- and GluR-A(PVCre-/-) mice. Experimental and modeling data indicated that this alteration could be accounted for by imprecise spike timing of fast-spiking cells (FS) caused by smaller interneuronal EPSPs. GluR-D-/- and GluR-A(PVCre-/-) mice exhibited similar impairments in hippocampus-dependent tasks. These findings directly show the effects of insufficient recruitment of fast-spiking cells at the network and behavioral level and demonstrate the role of this subpopulation for working and episodic-like memory.
由一组γ-氨基丁酸能中间神经元提供的胞周抑制在锥体细胞输出的定时中起关键作用。为了在网络和行为水平上测试它们的作用，我们培育了转基因小鼠，其中通过敲除GluR-D或通过有条件地切除小白蛋白阳性细胞中的GluR-A亚基来选择性降低兴奋性驱动。获得了可比的细胞类型特异性的AMPA介导电流减少。在来自GluR-D-/-和GluR-A(PVCre-/-)小鼠的海马切片中，海人酸诱导的γ振荡表现出功率降低。实验和建模数据表明，这种改变可以由较小的中间神经元兴奋性突触后电位导致的快速放电细胞（FS）的不精确峰电位定时来解释。GluR-D-/-和GluR-A(PVCre-/-)小鼠在依赖海马的任务中表现出类似的损伤。这些发现直接显示了在网络和行为水平上快速放电细胞募集不足的影响，并证明了这一亚群对工作记忆和情景样记忆的作用。
