Loss of limbic system-associated membrane protein leads to reduced hippocampal mineralocorticoid receptor expression, impaired synaptic plasticity, and spatial memory deficit.

Abstract

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.

• Authors: Shenfeng Qiu, Danielle L Champagne, Melinda Peters, Elizabeth H Catania, Edwin J Weeber, Pat Levitt, Aurea F Pimenta
• Journal: Biological psychiatry (Biol Psychiatry) Vol. 68 Issue 2 Pg. 197-204 (Jul 15 2010) ISSN: 1873-2402 [Electronic] United States
• PMID: 20385375 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Chemical References

• Cell Adhesion Molecules, Neuronal
• GPI-Linked Proteins
• Receptors, Mineralocorticoid
• limbic system-associated membrane protein
• Corticosterone

Topics

• Analysis of Variance
• Animals
• Behavior, Animal (physiology)
• Blotting, Western
• Cell Adhesion Molecules, Neuronal (genetics)
• Corticosterone (pharmacology)
• Electrophysiology
• GPI-Linked Proteins
• Hippocampus (drug effects, metabolism)
• Immunohistochemistry
• In Situ Hybridization
• Long-Term Potentiation (drug effects, genetics)
• Maze Learning (physiology)
• Mental Recall (physiology)
• Mice
• Mice, Knockout
• Neurons (metabolism)
• Receptors, Mineralocorticoid (genetics, metabolism)
• Spatial Behavior (physiology)
• Synapses (genetics, metabolism)