Journal Article

Deletion of Glutamate Delta-1 Receptor in Mouse Leads to Aberrant Emotional and Social Behaviors

Dravid, Shashank M., Yadav, Roopali, Bhatt, Jay M., Gupta, Subhash C., Stairs, Dustin J., Hillman, Brandon G.

2012

Overview

The delta family of ionotropic glutamate receptors consists of glutamate δ1 (GluD1) and glutamate δ2 (GluD2) receptors. While the role of GluD2 in the regulation of cerebellar physiology is well understood, the function of GluD1 in the central nervous system remains elusive. We demonstrate for the first time that deletion of GluD1 leads to abnormal emotional and social behaviors. We found that GluD1 knockout mice (GluD1 KO) were hyperactive, manifested lower anxiety-like behavior, depression-like behavior in a forced swim test and robust aggression in the resident-intruder test. Chronic lithium rescued the depression-like behavior in GluD1 KO. GluD1 KO mice also manifested deficits in social interaction. In the sociability test, GluD1 KO mice spent more time interacting with an inanimate object compared to a conspecific mouse. D-Cycloserine (DCS) administration was able to rescue social interaction deficits observed in GluD1 KO mice. At a molecular level synaptoneurosome preparations revealed lower GluA1 and GluA2 subunit expression in the prefrontal cortex and higher GluA1, GluK2 and PSD95 expression in the amygdala of GluD1 KO. Moreover, DCS normalized the lower GluA1 expression in prefrontal cortex of GluD1 KO. We propose that deletion of GluD1 leads to aberrant circuitry in prefrontal cortex and amygdala owing to its potential role in presynaptic differentiation and synapse formation. Furthermore, these findings are in agreement with the human genetic studies suggesting a strong association of GRID1 gene with several neuropsychiatric disorders including schizophrenia, bipolar disorder, autism spectrum disorders and major depressive disorder.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Aberration / Affective Symptoms - genetics / Aggression / Amygdala / Amygdala - metabolism / Animals / Anxiety / Anxiety - genetics / Autism / Behavior disorders / Behavior, Animal / Biology / Bipolar disorder / Brain research / Central nervous system / Cerebellum / Circuits / Cycloserine / Deletion / DELTA protein / Depression - drug therapy / Depression - genetics / Disorders / Emotional behavior / Gene Deletion / Gene Expression / Genes / Genomes / Glutamate / Glutamic acid receptors (ionotropic) / Hyperactivity / Kinases / Laboratory animals / Lithium / Lithium - administration & dosage / Lithium - pharmacology / Male / Mental depression / Mental disorders / Mice / Mice, 129 Strain / Mice, Inbred C57BL / Mice, Knockout / Mutation / Nervous system diseases / Pharmacology / Physiological aspects / Postsynaptic density proteins / Prefrontal cortex / Prefrontal Cortex - metabolism / Proteins / Receptors / Receptors, Glutamate - genetics / Rodents / Schizophrenia / Social aspects / Social behavior / Social Behavior Disorders - drug therapy / Social Behavior Disorders - genetics / Studies / Synapses / Synaptogenesis