A double hit mouse model of schizophrenia: Chronic stress impairs latent inhibition in CHL1 deficient mice
Class
Article
Department
Psychology
Faculty Mentor
Catalin Buhusi
Presentation Type
Poster Presentation
Abstract
Latent inhibition (LI) is an adaptive attentional phenomenon in which preexposure to a neutral stimulus decreases the future associability of the preexposed stimulus. LI is attenuated in patients with schizophrenia, and is reinstated by administration of typical antipsychotic medications. A number of gene polymorphisms have been found to be associated with an increased risk for the development of schizophrenia. The close homolog of L1 (CHL1) adhesion molecule is involved in brain development and plasticity. CHL1-deficient mice exhibit anatomical changes also observed in individuals with schizophrenia. In individuals with a genetic predisposition to schizophrenia it may be necessary for a precipitating event to occur, constituting a double hit, for symptoms of schizophrenia to appear. In this study, we have evaluated the effects of stress on inducing behavioral deficits characteristic of schizophrenia in CHL1 knockout mice (KO), heterozygous mice (HET), and wild type littermate controls (WT). Mice were divided into two groups: mice in the STRESS condition received chronic mild stress, while NO-STRESS mice were not manipulated. Upon reaching adulthood, all mice were tested in the LI paradigm as follows: Mice were repeatedly exposed to a preexposed (PE) stimulus. Following preexposure, a foot shock was paired with both the PE stimulus and a new, non-preexposed (NPE) stimulus. Conditioned freezing during the PE and NPE stimuli was then assessed following conditioning, and the results were analyzed statistically. The results indicate that preexposure reliably decreases freezing, and that the preexposure effect is reliably larger in the NO-STRESS condition. Most importantly, analyses also indicated a reliable interaction between stress and genotype: While KO mice in the NO-STRESS condition showed reliable LI, KO mice in the STRESS condition did not show LI, indicating an interaction between genotype and stress in latent inhibition, thus providing support for a double hit model of schizophrenia.
Start Date
4-9-2015 1:30 PM
A double hit mouse model of schizophrenia: Chronic stress impairs latent inhibition in CHL1 deficient mice
Latent inhibition (LI) is an adaptive attentional phenomenon in which preexposure to a neutral stimulus decreases the future associability of the preexposed stimulus. LI is attenuated in patients with schizophrenia, and is reinstated by administration of typical antipsychotic medications. A number of gene polymorphisms have been found to be associated with an increased risk for the development of schizophrenia. The close homolog of L1 (CHL1) adhesion molecule is involved in brain development and plasticity. CHL1-deficient mice exhibit anatomical changes also observed in individuals with schizophrenia. In individuals with a genetic predisposition to schizophrenia it may be necessary for a precipitating event to occur, constituting a double hit, for symptoms of schizophrenia to appear. In this study, we have evaluated the effects of stress on inducing behavioral deficits characteristic of schizophrenia in CHL1 knockout mice (KO), heterozygous mice (HET), and wild type littermate controls (WT). Mice were divided into two groups: mice in the STRESS condition received chronic mild stress, while NO-STRESS mice were not manipulated. Upon reaching adulthood, all mice were tested in the LI paradigm as follows: Mice were repeatedly exposed to a preexposed (PE) stimulus. Following preexposure, a foot shock was paired with both the PE stimulus and a new, non-preexposed (NPE) stimulus. Conditioned freezing during the PE and NPE stimuli was then assessed following conditioning, and the results were analyzed statistically. The results indicate that preexposure reliably decreases freezing, and that the preexposure effect is reliably larger in the NO-STRESS condition. Most importantly, analyses also indicated a reliable interaction between stress and genotype: While KO mice in the NO-STRESS condition showed reliable LI, KO mice in the STRESS condition did not show LI, indicating an interaction between genotype and stress in latent inhibition, thus providing support for a double hit model of schizophrenia.