Deletion of glutamate delta-1 receptor in mouse leads to aberrant emotional and social behaviors

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

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere32969
JournalPLoS One
Volume7
Issue number3
DOIs
StatePublished - Mar 7 2012

Fingerprint

Social Behavior
social behavior
Knockout Mice
glutamates
Cycloserine
Glutamic Acid
receptors
mice
Ionotropic Glutamate Receptors
Prefrontal Cortex
Physiology
Neurology
Lithium
Interpersonal Relations
Amygdala
cycloserine
Genes
amygdala
Depression
Major Depressive Disorder

All Science Journal Classification (ASJC) codes

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Deletion of glutamate delta-1 receptor in mouse leads to aberrant emotional and social behaviors. / Yadav, Roopali; Gupta, Subhash C.; Hillman, Brandon G.; Bhatt, Jay M.; Stairs, Dustin; Dravid, Shashank M.

In: PLoS One, Vol. 7, No. 3, e32969, 07.03.2012.

Research output: Contribution to journalArticle

Yadav, Roopali ; Gupta, Subhash C. ; Hillman, Brandon G. ; Bhatt, Jay M. ; Stairs, Dustin ; Dravid, Shashank M. / Deletion of glutamate delta-1 receptor in mouse leads to aberrant emotional and social behaviors. In: PLoS One. 2012 ; Vol. 7, No. 3.
@article{9d2c868b6c664a3781c8da4690a1c20a,
title = "Deletion of glutamate delta-1 receptor in mouse leads to aberrant emotional and social behaviors",
abstract = "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.",
author = "Roopali Yadav and Gupta, {Subhash C.} and Hillman, {Brandon G.} and Bhatt, {Jay M.} and Dustin Stairs and Dravid, {Shashank M.}",
year = "2012",
month = "3",
day = "7",
doi = "10.1371/journal.pone.0032969",
language = "English",
volume = "7",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3",

}

TY - JOUR

T1 - Deletion of glutamate delta-1 receptor in mouse leads to aberrant emotional and social behaviors

AU - Yadav, Roopali

AU - Gupta, Subhash C.

AU - Hillman, Brandon G.

AU - Bhatt, Jay M.

AU - Stairs, Dustin

AU - Dravid, Shashank M.

PY - 2012/3/7

Y1 - 2012/3/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84863279487&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863279487&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0032969

DO - 10.1371/journal.pone.0032969

M3 - Article

C2 - 22412961

AN - SCOPUS:84863279487

VL - 7

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 3

M1 - e32969

ER -