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Temporal and Regional Regulation of Gene Expression by Calcium-Stimulated Adenylyl Cyclase Activity during Fear Memory

BACKGROUND: The Ca2+-stimulated adenylyl cyclases (ACs), AC1 and AC8, are key components of long-term memory processing. AC1 and AC8 double knockout mice (Adcy1(−/−)Adcy8(−/−); DKO) display impaired fear memory processing; the mechanism of this impairment is largely unknown. METHODOLOGY/PRINCIPAL FI...

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Autores principales: Wieczorek, Lindsay, Maas, James W., Muglia, Lisa M., Vogt, Sherri K., Muglia, Louis J.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2954788/
https://www.ncbi.nlm.nih.gov/pubmed/20976279
http://dx.doi.org/10.1371/journal.pone.0013385
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author Wieczorek, Lindsay
Maas, James W.
Muglia, Lisa M.
Vogt, Sherri K.
Muglia, Louis J.
author_facet Wieczorek, Lindsay
Maas, James W.
Muglia, Lisa M.
Vogt, Sherri K.
Muglia, Louis J.
author_sort Wieczorek, Lindsay
collection PubMed
description BACKGROUND: The Ca2+-stimulated adenylyl cyclases (ACs), AC1 and AC8, are key components of long-term memory processing. AC1 and AC8 double knockout mice (Adcy1(−/−)Adcy8(−/−); DKO) display impaired fear memory processing; the mechanism of this impairment is largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: We hypothesize that the Ca2+-stimulated ACs modulate long-lasting transcriptional changes essential for fear memory consolidation and maintenance. Here, we report a genome-wide study of gene expression changes associated with conditioned fear (CF) memory in wild-type and DKO mice to identify AC-dependent gene regulatory changes that occur in the amygdala and hippocampus at baseline and different time points after CF learning. We observed an overall decrease in transcriptional changes in DKO mice across all time points, but most strikingly, at periods when memory consolidation and retention should be occurring. Further, we identified a shared set of transcription factor binding sites in genes upregulated in wild-type mice that were associated with downregulated genes in DKO mice. To prove the temporal and regional importance of AC activity on different stages of memory processing, the tetracycline-off system was used to produce mice with forebrain-specific inducible expression of AC8 on a DKO background. CF behavioral results reveal that adult restoration of AC8 activity in the forebrain is sufficient for intact learning, while cessation of this expression at any time point across learning causes memory deficits. CONCLUSIONS/SIGNIFICANCE: Overall, these studies demonstrate that the Ca2+-stimulated ACs contribute to the formation and maintenance of fear memory by a network of long-term transcriptional changes.
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spelling pubmed-29547882010-10-25 Temporal and Regional Regulation of Gene Expression by Calcium-Stimulated Adenylyl Cyclase Activity during Fear Memory Wieczorek, Lindsay Maas, James W. Muglia, Lisa M. Vogt, Sherri K. Muglia, Louis J. PLoS One Research Article BACKGROUND: The Ca2+-stimulated adenylyl cyclases (ACs), AC1 and AC8, are key components of long-term memory processing. AC1 and AC8 double knockout mice (Adcy1(−/−)Adcy8(−/−); DKO) display impaired fear memory processing; the mechanism of this impairment is largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: We hypothesize that the Ca2+-stimulated ACs modulate long-lasting transcriptional changes essential for fear memory consolidation and maintenance. Here, we report a genome-wide study of gene expression changes associated with conditioned fear (CF) memory in wild-type and DKO mice to identify AC-dependent gene regulatory changes that occur in the amygdala and hippocampus at baseline and different time points after CF learning. We observed an overall decrease in transcriptional changes in DKO mice across all time points, but most strikingly, at periods when memory consolidation and retention should be occurring. Further, we identified a shared set of transcription factor binding sites in genes upregulated in wild-type mice that were associated with downregulated genes in DKO mice. To prove the temporal and regional importance of AC activity on different stages of memory processing, the tetracycline-off system was used to produce mice with forebrain-specific inducible expression of AC8 on a DKO background. CF behavioral results reveal that adult restoration of AC8 activity in the forebrain is sufficient for intact learning, while cessation of this expression at any time point across learning causes memory deficits. CONCLUSIONS/SIGNIFICANCE: Overall, these studies demonstrate that the Ca2+-stimulated ACs contribute to the formation and maintenance of fear memory by a network of long-term transcriptional changes. Public Library of Science 2010-10-14 /pmc/articles/PMC2954788/ /pubmed/20976279 http://dx.doi.org/10.1371/journal.pone.0013385 Text en Wieczorek et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Wieczorek, Lindsay
Maas, James W.
Muglia, Lisa M.
Vogt, Sherri K.
Muglia, Louis J.
Temporal and Regional Regulation of Gene Expression by Calcium-Stimulated Adenylyl Cyclase Activity during Fear Memory
title Temporal and Regional Regulation of Gene Expression by Calcium-Stimulated Adenylyl Cyclase Activity during Fear Memory
title_full Temporal and Regional Regulation of Gene Expression by Calcium-Stimulated Adenylyl Cyclase Activity during Fear Memory
title_fullStr Temporal and Regional Regulation of Gene Expression by Calcium-Stimulated Adenylyl Cyclase Activity during Fear Memory
title_full_unstemmed Temporal and Regional Regulation of Gene Expression by Calcium-Stimulated Adenylyl Cyclase Activity during Fear Memory
title_short Temporal and Regional Regulation of Gene Expression by Calcium-Stimulated Adenylyl Cyclase Activity during Fear Memory
title_sort temporal and regional regulation of gene expression by calcium-stimulated adenylyl cyclase activity during fear memory
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2954788/
https://www.ncbi.nlm.nih.gov/pubmed/20976279
http://dx.doi.org/10.1371/journal.pone.0013385
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