期刊
BIOLOGICAL PSYCHIATRY
卷 68, 期 2, 页码 197-204出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2010.02.013
关键词
Limbic system-associated membrane protein; mineralocorticoid receptor; spatial memory; stress; synaptic plasticity
资金
- National Institute of Mental Health [MH45507]
- Vanderbilt Kennedy Center Core Grant National Institute of Child Health and Human Development [HD15052]
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.
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