Genetic Deletion of Lsamp Causes Exaggerated Behavioral Activation in Novel Environments

Abstract

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.

A novel microdeletion syndrome at 3q13.31 characterised by developmental delay, postnatal overgrowth, hypoplastic male genitals, and characteristic facial features

“…First, the deletion in case 14, telomeric of the SRO, contains LSAMP and GAP43 , two strong candidate genes for developmental delay. LSAMP encodes the limbic system associated membrane protein, and studies in both human and mice models have demonstrated the involvement of LSAMP in neuropsychiatric features and behaviour 30 31. GAP43 is involved in neurite outgrowth, neurotransmission, and synaptic plasticity among other functions and GAP43 was also recently identified as a candidate gene for autism and autistic-like manifestations in human and mice 32–34.…”

Voltage-Gated Na+Channel β1B: A Secreted Cell Adhesion Molecule Involved in Human Epilepsy

“…Deletion of Nr-CAM in mice results in an altered behavioral phenotype reflective of increased impulsivity (Matzel, et al 2008). Deletion of the CAM Lsamp in mice leads to heightened reactivity to novelty (Catania, et al 2008) and conditional deletion of L1-CAM in brain results in decreased anxiety-like behavior (Law, et al 2003). Epilepsy and neuropsychiatric disease have a bidirectional relationship of comorbidity (Dixon-Salazar, et al 2004; Gargus 2006; Jacoby and Thapar 2009; Pauli and Stefan 2009; Spence and Schneider 2009) and thus may share common genetic mechanisms.…”

Rapid non-genomic effects of corticosteroids and their role in the central stress response

“…This comes from a study using knockout mice for the limbic system-associated membrane protein (LSAMP). These mice showed increased novelty reactivity and impaired learning (Catania et al 2008, Qiu et al 2010, and associated with this, a reduction in non-genomic MR function in the hippocampus (Qiu et al 2010).…”