Journal Article

GluD1 knockout mice with a pure C57BL/6N background show impaired fear memory, social interaction, and enhanced depressive-like behavior

Nakamoto, Chihiro, Kawamura, Meiko, Takao, Keizo, Nakatsukasa, Ena, Takeuchi, Tomonori, Abe, Manabu, Sakimura, Kenji, Natsume, Rie, Watanabe, Masahiko

2020

Overview

The GluD1 gene is associated with susceptibility for schizophrenia, autism, depression, and bipolar disorder. However, the function of GluD1 and how it is involved in these conditions remain elusive. In this study, we generated a Grid1 gene-knockout (GluD1-KO) mouse line with a pure C57BL/6N genetic background and performed several behavioral analyses. Compared to a control group, GluD1-KO mice showed no significant anxiety-related behavioral differences, evaluated using behavior in an open field, elevated plus maze, a light-dark transition test, the resident-intruder test of aggression and sensorimotor gating evaluated by the prepulse inhibition test. However, GluD1-KO mice showed (1) higher locomotor activity in the open field, (2) decreased sociability and social novelty preference in the three-chambered social interaction test, (3) impaired memory in contextual, but not cued fear conditioning tests, and (4) enhanced depressive-like behavior in a forced swim test. Pharmacological studies revealed that enhanced depressive-like behavior in GluD1-KO mice was restored by the serotonin reuptake inhibitors imipramine and fluoxetine, but not the norepinephrine transporter inhibitor desipramine. In addition, biochemical analysis revealed no significant difference in protein expression levels, such as other glutamate receptors in the synaptosome and postsynaptic densities prepared from the frontal cortex and the hippocampus. These results suggest that GluD1 plays critical roles in fear memory, sociability, and depressive-like behavior.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animals / Antidepressants / Anxiety / Anxiety - etiology / Anxiety - pathology / Autism / Behavior / Behavior, Animal / Biochemical analysis / Biology and Life Sciences / Bipolar disorder / Brain / Brain research / Channel gating / Comparative analysis / Cortex (frontal) / Depression - etiology / Depression - pathology / Desipramine / Disease susceptibility / Fear / Fear conditioning / Fluoxetine / Gene expression / Genes / Genetic analysis / Genetic aspects / Glutamate / Glutamate Dehydrogenase - physiology / Glutamate receptors / Glutamic acid receptors / House mouse / Imipramine / Interpersonal Relations / Life sciences / Light / Locomotor activity / Male / Medicine and Health Sciences / Memory / Memory Disorders - etiology / Memory Disorders - pathology / Mental depression / Mental disorders / Methods / Mice / Mice, Inbred C57BL / Mice, Knockout / Motor Activity / Neomycin / Neurosciences / Norepinephrine / Norepinephrine transporter / Open-field behavior / Phenols (Class of compounds) / Receptors / Research and Analysis Methods / Schizophrenia / Sensorimotor gating / Serotonin / Serotonin uptake inhibitors / Social aspects / Social behavior / Social Behavior Disorders - etiology / Social Behavior Disorders - pathology / Social factors / Social Sciences