Loss of limbic system-associated membrane protein leads to reduced hippocampal mineralocorticoid receptor expression, impaired synaptic plasticity, and spatial memory deficit.
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.
Qiu
Shenfeng
S
Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232-8548, USA.
Champagne
Danielle L
DL
Peters
Melinda
M
Catania
Elizabeth H
EH
Weeber
Edwin J
EJ
Levitt
Pat
P
Pimenta
Aurea F
AF
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015153:Blotting, Western; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D003345:Corticosterone / Q000494:pharmacology; D004594:Electrophysiology; D058851:GPI-Linked Proteins; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics*; D018782:Maze Learning / Q000502:physiology*; D011939:Mental Recall / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism*; D013037:Spatial Behavior / Q000502:physiology; D013569:Synapses / Q000235:genetics / Q000378:metabolism
D015816:Cell Adhesion Molecules, Neuronal; D058851:GPI-Linked Proteins; D018161:Receptors, Mineralocorticoid; C095362:limbic system-associated membrane protein; D003345:Corticosterone
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