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

Qiu, Shenfeng; Champagne, Danielle L.; Peters, Melinda; Catania, Elizabeth H.; Weeber, Edwin J.; Levitt, Pat; Pimenta, Aurea F.

doi:10.1016/j.biopsych.2010.02.013

« Previous Next »Biological Psychiatry
Volume 68, Issue 2 , Pages 197-204, 15 July 2010

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

Shenfeng Qiu
- Department of Pharmacology, Vanderbilt University, Nashville, Tennessee
- Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, Tennessee
Danielle L. Champagne
- Leiden/Amsterdam Center for Drug Research, Leiden, Netherlands
Melinda Peters
- Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida
Elizabeth H. Catania
- Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, Tennessee
Edwin J. Weeber
- Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida
Pat Levitt
- Department of Pharmacology, Vanderbilt University, Nashville, Tennessee
- Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, Tennessee
Aurea F. Pimenta
- Department of Pharmacology, Vanderbilt University, Nashville, Tennessee
- Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, Tennessee
- Address correspondence to Aurea F. Pimenta, Ph.D., Department of Pharmacology and Vanderbilt Kennedy Center for Research on Human Development, 8114C MRB III, 465 21st Avenue South, Nashville, TN 37232-8548

Received 9 October 2009; received in revised form 10 February 2010; accepted 12 February 2010. published online 13 April 2010.

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.

Key Words: Limbic system-associated membrane protein, mineralocorticoid receptor, spatial memory, stress, synaptic plasticity