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母性关怀与海马可塑性:经验依赖性结构可塑性、突触功能改变以及对糖皮质激素和应激反应差异的证据

Maternal care and hippocampal plasticity: evidence for experience-dependent structural plasticity, altered synaptic functioning, and differential responsiveness to glucocorticoids and stress.

作者信息

Champagne Danielle L, Bagot Rosemary C, van Hasselt Felisa, Ramakers Ger, Meaney Michael J, de Kloet E Ronald, Joëls Marian, Krugers Harm

机构信息

Swammerdam Institute for Life Sciences Center for Neuroscience, University of Amsterdam, 1098 SM Amsterdam, The Netherlands.

出版信息

J Neurosci. 2008 Jun 4;28(23):6037-45. doi: 10.1523/JNEUROSCI.0526-08.2008.

Abstract

Maternal licking and grooming (LG) in infancy influences stress responsiveness and cognitive performance in the offspring. We examined the effects of variation in the frequency of pup LG on morphological, electrophysiological, and behavioral aspects of hippocampal synaptic plasticity under basal and stress-like conditions. We found shorter dendritic branch length and lower spine density in CA1 cells from the adult offspring of low compared with high LG offspring. We also observed dramatic effects on long-term potentiation (LTP) depending on corticosterone treatment. Low LG offspring, in contrast to those of high LG mothers, displayed significantly impaired LTP under basal conditions but surprisingly a significantly enhanced LTP in response to high corticosterone in vitro. This enhanced plasticity under conditions that mimic those of a stressful event was apparent in vivo. Adult low LG offspring displayed enhanced memory relative to high LG offspring when tested in a hippocampal-dependent, contextual fear-conditioning paradigm. Hippocampal levels of glucocorticoid and mineralocorticoid receptors were reduced in low compared with high LG offspring. Such effects, as well as the differences in dendritic morphology, likely contribute to LTP differences under resting conditions, as well as to the maternal effects on synaptic plasticity and behavior in response to elevated corticosterone levels. These results suggest that maternal effects may modulate optimal cognitive functioning in environments varying in demand in later life, with offspring of high and low LG mothers showing enhanced learning under contexts of low and high stress, respectively.

摘要

母体在幼年期的舔舐和梳理行为(LG)会影响后代的应激反应能力和认知表现。我们研究了幼崽LG频率变化对基础状态和应激样条件下海马突触可塑性的形态学、电生理学及行为学方面的影响。我们发现,与高LG后代的成年子代相比,低LG后代的CA1细胞中树突分支长度较短,棘突密度较低。我们还观察到,根据皮质酮处理情况,对长时程增强(LTP)有显著影响。与高LG母亲的后代相比,低LG后代在基础条件下LTP显著受损,但令人惊讶的是,在体外给予高皮质酮时LTP显著增强。这种在模拟应激事件条件下增强的可塑性在体内也很明显。在海马依赖性情境恐惧条件范式测试中,成年低LG后代相对于高LG后代表现出增强的记忆。与高LG后代相比,低LG后代海马中的糖皮质激素和盐皮质激素受体水平降低。这些影响以及树突形态的差异,可能导致了静息条件下LTP的差异,以及母体对应激皮质酮水平升高时突触可塑性和行为的影响。这些结果表明,母体效应可能会调节后代在不同需求环境中的最佳认知功能,高LG和低LG母亲的后代分别在低应激和高应激环境下表现出增强的学习能力。

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