The limbic system-associated membrane protein (LAMP) is a GPI-anchored cell adhesion molecule expressed heavily in limbic and limbic-associated regions of the developing and adult brain. Experimental studies show that LAMP promotes the growth of limbic neurons and guides the projections of limbic fibers. In order to examine the functional consequences of disrupting limbic circuit assembly, we generated a mouse line in which the Lsamp gene encoding LAMP was deleted. Basic neuroanatomical organization and sensory and motor development are normal in Lsamp −/− mice. The most profound change in behavior in both male and female Lsamp −/− mice is a heightened reactivity to novelty exhibited in several behavioral tests. Lsamp −/− mice display hyperactivity in a novel arena and both sexes habituate to the same activity levels as their wildtype littermates, but at different rates. In the elevated plus maze, Lsamp −/− mice exhibit increased total arm entries, with a bias towards the open arms; they spend more time in the open arms and have a substantial increase in the amount of risk assessment in unprotected areas of the maze. In the y-maze, Lsamp −/− mice exhibit characteristic hyperactivity and a decreased level of spontaneous alternation during the period when their novelty-induced hyperactivity is at its peak. We hypothesize that Lsamp −/− mice may not simply exhibit a decrease in anxiety, but may have a heightened, and possibly maladaptive, response to novel environmental stressors. Genetic deletion of Lsamp may thus cause circumscribed changes in the fine connectivity of specific circuits that underlie these behaviors.

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 controls. Results Lsamp−/− mice exhibit a pronounced deficit in spatial memory acquisition and poorly sustained CA1 long-term potentiation (LTP). We found reduced expression of mineralocorticoid receptor (MR) transcripts in the hippocampus, and reduction in the corticosterone-induced, MR-mediated non-genomic modulatory effects on CA1 synaptic transmission. Importantly, the impaired LTP 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.

Water shrews (Sorex palustris) depend heavily on their elaborate whiskers to navigate their environment and locate prey. They have small eyes and ears with correspondingly small optic and auditory nerves. Previous investigations have shown that water shrew neocortex is dominated by large representations of the whiskers in primary and secondary somatosensory cortex (S1 and S2). Flattened sections of juvenile cortex processed for cytochrome oxidase revealed clear borders of the whisker pad representation in S1, but no cortical barrels. We were therefore surprised to discover prominent barrelettes in brainstem of juvenile water shrews in the present investigation. These distinctive modules were found in the principal trigeminal nucleus (PrV), and in two of the three spinal trigeminal subnuclei (interpolaris – SpVi and caudalis – SpVc). Analysis of the shrew's whisker pad revealed the likely relationship between whiskers and barrelettes. Barrelettes persisted in adult water shrew PrV, but barrels were also absent from adult cortex. Thus in contrast to mice and rats, which have obvious barrels in primary somatosensory cortex and less clear barrelettes in the principal nucleus, water shrews have clear barrelettes in the brainstem and no barrels in the neocortex. These results highlight the diverse ways that similar mechanoreceptors can be represented in the central nervous systems of different species.

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