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

BackgroundThe 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.MethodsWe tested spatial memory performance, hippocampal synaptic plasticity, and stress-related modalities in Lsamp−/− mice and their littermate control mice.ResultsLsamp−/− 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.ConclusionsOur study reveals a novel functional relationship between a cell adhesion molecule enriched in developing limbic circuits, glucocorticoid receptors, and cognitive functioning.