Emotional regulation and the limbic system associated membrane protein

Abstract

Many neuropsychiatric disorders involve disruptions in emotional regulation that are correlated with dysfunctions in the limbic circuitry of the brain. Improved treatment and outcome of disorders of emotional regulation will come from understanding both the changes in brain signaling that underlie the behavioral and physiological components of the disorders and the origin of those changes. The limbic system associated membrane protein (protein: LAMP, gene: Lsamp) is of interest to the study of the biological mechanisms of emotional regulation because it is a developmentally relevant cell adhesion molecule expressed primarily in limbic circuitry and human genetic studies have implicated Lsamp in disorders of mood. We developed mice in which the Lsamp gene is deleted, creating a unique model to examine the functional consequences of disrupting the circuits that underlie emotional regulation. Basic neuroanatomical organization and sensory and motor development are normal in Lsamp_/_ mice. However, both male and female Lsamp-/- mice demonstrate heightened behavioral reactivity to novelty. Lsamp-/- mice also display heightened reactivity of the hypothalamic-pituitary-adrenal axis in response to a novel environment and a corresponding hyper-activation of brain circuitry that regulates the stress response. Preliminary data suggests that Lsamp-/- mice may have alterations in GABAergic tone and signaling, which could be responsible for the changes in stress-responsiveness observed in Lsamp-/- mice. These studies establish a role for LAMP in modulating the development and function of the circuitry that mediates emotional regulation.