Deletion of glutamate delta-1 receptor in mouse leads to enhanced working memory and deficit in fear conditioning.

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 be...

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Autores principales: Roopali Yadav, Brandon G Hillman, Subhash C Gupta, Pratyush Suryavanshi, Jay M Bhatt, Ratnamala Pavuluri, Dustin J Stairs, Shashank M Dravid
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/fa7bf2db766c45bb9bc72fda9a57b7b2
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spelling oai:doaj.org-article:fa7bf2db766c45bb9bc72fda9a57b7b22021-11-18T07:50:50ZDeletion of glutamate delta-1 receptor in mouse leads to enhanced working memory and deficit in fear conditioning.1932-620310.1371/journal.pone.0060785https://doaj.org/article/fa7bf2db766c45bb9bc72fda9a57b7b22013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23560106/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Glutamate 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.Roopali YadavBrandon G HillmanSubhash C GuptaPratyush SuryavanshiJay M BhattRatnamala PavuluriDustin J StairsShashank M DravidPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e60785 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Roopali Yadav
Brandon G Hillman
Subhash C Gupta
Pratyush Suryavanshi
Jay M Bhatt
Ratnamala Pavuluri
Dustin J Stairs
Shashank M Dravid
Deletion of glutamate delta-1 receptor in mouse leads to enhanced working memory and deficit in fear conditioning.
description 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.
format article
author Roopali Yadav
Brandon G Hillman
Subhash C Gupta
Pratyush Suryavanshi
Jay M Bhatt
Ratnamala Pavuluri
Dustin J Stairs
Shashank M Dravid
author_facet Roopali Yadav
Brandon G Hillman
Subhash C Gupta
Pratyush Suryavanshi
Jay M Bhatt
Ratnamala Pavuluri
Dustin J Stairs
Shashank M Dravid
author_sort Roopali Yadav
title Deletion of glutamate delta-1 receptor in mouse leads to enhanced working memory and deficit in fear conditioning.
title_short Deletion of glutamate delta-1 receptor in mouse leads to enhanced working memory and deficit in fear conditioning.
title_full Deletion of glutamate delta-1 receptor in mouse leads to enhanced working memory and deficit in fear conditioning.
title_fullStr Deletion of glutamate delta-1 receptor in mouse leads to enhanced working memory and deficit in fear conditioning.
title_full_unstemmed Deletion of glutamate delta-1 receptor in mouse leads to enhanced working memory and deficit in fear conditioning.
title_sort deletion of glutamate delta-1 receptor in mouse leads to enhanced working memory and deficit in fear conditioning.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/fa7bf2db766c45bb9bc72fda9a57b7b2
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