Gordon Joshua A, Lacefield Clay O, Kentros Clifford G, Hen Rene
Center for Neurobiology and Behavior, Department of Psychiatry, Columbia University, New York, New York 10032, USA.
J Neurosci. 2005 Jul 13;25(28):6509-19. doi: 10.1523/JNEUROSCI.1211-05.2005.
Mice lacking the serotonin 1A receptor (5-HT(1A)R) show increased levels of anxiety-related behavior across multiple tests and background strains. Tissue-specific rescue experiments, lesion studies, and neurophysiological findings all point toward the hippocampus as a potential mediator of the phenotype. Serotonin, acting through 5-HT(1A)Rs, can suppress hippocampal theta-frequency oscillations, suggesting that theta oscillations might be increased in the knock-outs. To test this hypothesis, local field potential recordings were obtained from the hippocampus of awake, behaving knock-outs and wild-type littermates. The magnitude of theta oscillations was increased in the knock-outs, specifically in the anxiety-provoking elevated plus maze and not in a familiar environment or during rapid eye movement sleep. Theta power correlated with the fraction of time spent in the open arms, an anxiety-related behavioral variable. These results suggest a possible role for the hippocampus, and theta oscillations in particular, in the expression of anxiety in 5-HT(1A)R-deficient mice.
缺乏5-羟色胺1A受体（5-HT(1A)R）的小鼠在多项测试和不同背景品系中均表现出焦虑相关行为水平升高。组织特异性拯救实验、损伤研究以及神经生理学研究结果均表明，海马体可能是该表型的潜在介导因素。5-羟色胺通过5-HT(1A)R发挥作用，可抑制海马体θ波频率振荡，这表明基因敲除小鼠的θ波振荡可能会增强。为验证这一假设，研究人员从清醒且有行为活动的基因敲除小鼠及野生型同窝小鼠的海马体中获取了局部场电位记录。基因敲除小鼠的θ波振荡幅度增加，特别是在引发焦虑的高架十字迷宫中，而在熟悉环境或快速眼动睡眠期间则未增加。θ波功率与在开放臂中停留时间的比例相关，这是一个与焦虑相关的行为变量。这些结果表明，海马体，尤其是θ波振荡，在5-HT(1A)R缺陷小鼠的焦虑表达中可能发挥作用。
