Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
Cereb Cortex. 2010 Nov;20(11):2712-27. doi: 10.1093/cercor/bhq017. Epub 2010 Mar 1.
The balance between excitation and inhibition controls fundamental aspects of the hippocampal function. Here, we report an increase in the ratio of inhibitory to excitatory neurons in the dentate gyrus, accompanied by γ-aminobutyric acid(A) (GABA(A)) receptor-dependent impairment of synaptic plasticity and enhancement of activity-dependent changes in excitability in anesthetized adult mice deficient for the extracellular matrix glycoprotein tenascin-R (TNR). TNR-deficient mice showed faster reversal learning, improved working memory, and enhanced reactivity to novelty than wild-type littermates. Remarkably, in wild-type and TNR-deficient mice, faster reversal learning rates correlated at the individual animal level with ratios of parvalbumin-positive interneurons to granule cells and densities of parvalbumin-positive terminals on somata of granule cells. Our data demonstrate that modification of the extracellular matrix by ablation of TNR leads to a new structural and functional design of the dentate gyrus, with enhanced GABAergic innervation, that is, enhanced ratio of inhibitory to excitatory cells, and altered plasticity, promoting working memory and reversal learning. In wild-type mice, the enhanced ratio of inhibitory to excitatory cells in the dentate gyrus also positively correlated with reversal learning, indicating that level of inhibition regulates specific aspects of learning independent of the TNR gene.
兴奋与抑制的平衡控制着海马体功能的基本方面。在这里，我们报告在齿状回中抑制性神经元与兴奋性神经元的比例增加，伴随着 γ-氨基丁酸(A)（GABA(A)）受体依赖性突触可塑性受损和麻醉成年 TNR 缺失型（tenascin-R）小鼠兴奋性变化增强。TNR 缺失型小鼠在反转学习、工作记忆和对新奇事物的反应方面表现出比野生型同窝仔鼠更快的速度。值得注意的是，在野生型和 TNR 缺失型小鼠中，更快的反转学习率在个体动物水平上与颗粒细胞中 parvalbumin 阳性中间神经元与颗粒细胞的比例以及颗粒细胞体上 parvalbumin 阳性终末的密度相关。我们的数据表明，通过消融 TNR 来修饰细胞外基质会导致齿状回的新的结构和功能设计，增强 GABA 能神经支配，即增强抑制性与兴奋性细胞的比率，并改变可塑性，促进工作记忆和反转学习。在野生型小鼠中，齿状回中抑制性神经元与兴奋性神经元的比率增加也与反转学习呈正相关，表明抑制水平调节着学习的特定方面，与 TNR 基因无关。
