Loss of Limbic System-Associated Membrane Protein Leads to Reduced Hippocampal Mineralocorticoid Receptor Expression, Impaired Synaptic Plasticity, and Spatial Memory Deficit

被引:42
作者
Qiu, Shenfeng [1 ,2 ]
Champagne, Danielle L. [3 ]
Peters, Melinda [4 ]
Catania, Elizabeth H. [2 ]
Weeber, Edwin J. [4 ]
Levitt, Pat [1 ,2 ]
Pimenta, Aurea F. [1 ,2 ]
机构
[1] Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Vanderbilt Kennedy Ctr Res Human Dev, Nashville, TN 37232 USA
[3] Leiden Amsterdam Ctr Drug Res, Leiden, Netherlands
[4] Univ S Florida, Tampa, FL USA
关键词
Limbic system-associated membrane protein; mineralocorticoid receptor; spatial memory; stress; synaptic plasticity; LONG-TERM POTENTIATION; GLUCOCORTICOID-RECEPTORS; EXPLORATORY ACTIVITY; BRAIN-REGIONS; WATER-MAZE; IN-VITRO; STRESS; RAT; CORTICOSTERONE; TRAFFICKING;
D O I
10.1016/j.biopsych.2010.02.013
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Background: The limbic system-associated membrane protein (LAMP) promotes development of neurons of limbic origin. We have previously shown that genetic deletion of LAMP results in heightened reactivity to novelty and reduced anxiety-like behaviors in mice. Here, we demonstrate a critical role of LAMP in hippocampal-dependent synaptic physiology and behavior. Methods: We tested spatial memory performance, hippocampal synaptic plasticity, and stress-related modalities in Lsamp(-/-) mice and their littermate control mice. Results: Lsamp(-/-) mice exhibit a pronounced deficit in spatial memory acquisition and poorly sustained CA1 long-term potentiation. We found reduced expression of mineralocorticoid receptor (MR) transcripts in the hippocampus and reduction in the corticosterone-induced, MR-mediated nongenomic modulatory effects on CA1 synaptic transmission. Importantly, the impaired long-term potentiation in Lsamp(-/-) mice can be rescued by stress-like levels of corticosterone in a MR-dependent manner. Conclusions: Our study reveals a novel functional relationship between a cell adhesion molecule enriched in developing limbic circuits, glucocorticoid receptors, and cognitive functioning.
引用
收藏
页码:197 / 204
页数:8
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