Deletion of Glutamate Delta-1 Receptor in Mouse Leads to Enhanced Working Memory and Deficit in Fear Conditioning

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

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Glutamate delta-1 (GluD1) receptors are expressed throughout the forebrain during development with high levels in the hippocampus during adulthood. We have recently shown that deletion of GluD1 receptor results in aberrant emotional and social behaviors such as hyperaggression and depression-like behaviors and social interaction deficits. Additionally, abnormal expression of synaptic proteins was observed in amygdala and prefrontal cortex of GluD1 knockout mice (GluD1 KO). However the role of GluD1 in learning and memory paradigms remains unknown. In the present study we evaluated GluD1 KO in learning and memory tests. In the eight-arm radial maze GluD1 KO mice committed fewer working memory errors compared to wildtype mice but had normal reference memory. Enhanced working memory in GluD1 KO was also evident by greater percent alternation in the spontaneous Y-maze test. No difference was observed in object recognition memory in the GluD1 KO mice. In the Morris water maze test GluD1 KO mice showed no difference in acquisition but had longer latency to find the platform in the reversal learning task. GluD1 KO mice showed a deficit in contextual and cue fear conditioning but had normal latent inhibition. The deficit in contextual fear conditioning was reversed by D-Cycloserine (DCS) treatment. GluD1 KO mice were also found to be more sensitive to foot-shock compared to wildtype. We further studied molecular changes in the hippocampus, where we found lower levels of GluA1, GluA2 and GluK2 subunits while a contrasting higher level of GluN2B in GluD1 KO. Additionally, we found higher postsynaptic density protein 95 (PSD95) and lower glutamate decarboxylase 67 (GAD67) expression in GluD1 KO. We propose that GluD1 is crucial for normal functioning of synapses and absence of GluD1 leads to specific abnormalities in learning and memory. These findings provide novel insights into the role of GluD1 receptors in the central nervous system.

Original languageEnglish
Article numbere60785
JournalPLoS One
Volume8
Issue number4
DOIs
StatePublished - Apr 3 2013

Fingerprint

Memory Disorders
conditioned behavior
fearfulness
Short-Term Memory
glutamates
Fear
Glutamic Acid
Data storage equipment
receptors
mice
learning
Learning
Conditioning (Psychology)
glutamate receptor delta 1
hippocampus
Hippocampus
Reversal Learning
Cycloserine
cycloserine
Glutamate Decarboxylase

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 Enhanced Working Memory and Deficit in Fear Conditioning. / Yadav, Roopali; Hillman, Brandon G.; Gupta, Subhash C.; Suryavanshi, Pratyush; Bhatt, Jay M.; Pavuluri, Ratnamala; Stairs, Dustin; Dravid, Shashank M.

In: PLoS One, Vol. 8, No. 4, e60785, 03.04.2013.

Research output: Contribution to journalArticle

Yadav, Roopali ; Hillman, Brandon G. ; Gupta, Subhash C. ; Suryavanshi, Pratyush ; Bhatt, Jay M. ; Pavuluri, Ratnamala ; Stairs, Dustin ; Dravid, Shashank M. / Deletion of Glutamate Delta-1 Receptor in Mouse Leads to Enhanced Working Memory and Deficit in Fear Conditioning. In: PLoS One. 2013 ; Vol. 8, No. 4.
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