Inducible forebrain-specific ablation of the transcription factor Creb during adulthood induces anxiety but no spatial/contextual learning deficits
The cyclic AMP (cAMP)-response element binding protein (CREB) is an activity-dependent transcription factor playing a role in synaptic plasticity, learning and memory, and emotional behavior. However, the impact of Creb ablation on rodent behavior is vague as e.g. memory performance of different Cre...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-11-01
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| Series: | Frontiers in Behavioral Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnbeh.2014.00407/full |
| _version_ | 1811315215009054720 |
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| author | Miriam Annika Vogt Dragos eInta Alessia eLuoni Hasan eElkin Natascha ePfeiffer Marco Andrea Riva Peter eGass |
| author_facet | Miriam Annika Vogt Dragos eInta Alessia eLuoni Hasan eElkin Natascha ePfeiffer Marco Andrea Riva Peter eGass |
| author_sort | Miriam Annika Vogt |
| collection | DOAJ |
| description | The cyclic AMP (cAMP)-response element binding protein (CREB) is an activity-dependent transcription factor playing a role in synaptic plasticity, learning and memory, and emotional behavior. However, the impact of Creb ablation on rodent behavior is vague as e.g. memory performance of different Creb mutant mice depends on the specific type of mutation per se but additionally on the background and learning protocol differences. Here we present the first targeted ablation of CREB induced during adulthood selectively in principal forebrain neurons in a pure background strain of C57BL/6 mice. All hippocampal principal neurons exhibited lack of CREB expression. Mutant mice showed a severe anxiety phenotype in the openfield and novel object exploration test as well as in the Dark-Light Box Test, but unaltered hippocampus-dependent long-term memory in the Morris water maze and in context dependent fear conditioning. On the molecular level, CREB ablation led to CREM up regulation in the hippocampus and frontal cortex which may at least in part compensate for the loss of CREB. BDNF, a postulated CREB target gene, was down regulated in the frontal lobe but not in the hippocampus; neurogenesis remained unaltered. Our data indicate that in the adult mouse forebrain the late onset of CREB ablation can, in case of memory functionality, be compensated for and is not essential for memory consolidation and retrieval during adulthood. In contrast, the presence of CREB protein during adulthood seems to be pivotal for the regulation of emotional behavior. |
| first_indexed | 2024-04-13T11:27:30Z |
| format | Article |
| id | doaj.art-62330a55358648bd9a3341fb97438e4f |
| institution | Directory Open Access Journal |
| issn | 1662-5153 |
| language | English |
| last_indexed | 2024-04-13T11:27:30Z |
| publishDate | 2014-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Behavioral Neuroscience |
| spelling | doaj.art-62330a55358648bd9a3341fb97438e4f2022-12-22T02:48:40ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532014-11-01810.3389/fnbeh.2014.00407110543Inducible forebrain-specific ablation of the transcription factor Creb during adulthood induces anxiety but no spatial/contextual learning deficitsMiriam Annika Vogt0Dragos eInta1Alessia eLuoni2Hasan eElkin3Natascha ePfeiffer4Marco Andrea Riva5Peter eGass6Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg UniversityCentral Institute of Mental Health, Medical Faculty Mannheim/Heidelberg UniversityUniversity of MilanCentral Institute of Mental Health, Medical Faculty Mannheim/Heidelberg UniversityCentral Institute of Mental Health, Medical Faculty Mannheim/Heidelberg UniversityUniversity of MilanCentral Institute of Mental Health, Medical Faculty Mannheim/Heidelberg UniversityThe cyclic AMP (cAMP)-response element binding protein (CREB) is an activity-dependent transcription factor playing a role in synaptic plasticity, learning and memory, and emotional behavior. However, the impact of Creb ablation on rodent behavior is vague as e.g. memory performance of different Creb mutant mice depends on the specific type of mutation per se but additionally on the background and learning protocol differences. Here we present the first targeted ablation of CREB induced during adulthood selectively in principal forebrain neurons in a pure background strain of C57BL/6 mice. All hippocampal principal neurons exhibited lack of CREB expression. Mutant mice showed a severe anxiety phenotype in the openfield and novel object exploration test as well as in the Dark-Light Box Test, but unaltered hippocampus-dependent long-term memory in the Morris water maze and in context dependent fear conditioning. On the molecular level, CREB ablation led to CREM up regulation in the hippocampus and frontal cortex which may at least in part compensate for the loss of CREB. BDNF, a postulated CREB target gene, was down regulated in the frontal lobe but not in the hippocampus; neurogenesis remained unaltered. Our data indicate that in the adult mouse forebrain the late onset of CREB ablation can, in case of memory functionality, be compensated for and is not essential for memory consolidation and retrieval during adulthood. In contrast, the presence of CREB protein during adulthood seems to be pivotal for the regulation of emotional behavior.http://journal.frontiersin.org/Journal/10.3389/fnbeh.2014.00407/fullAnxietyLearningMemoryBDNFMouseCREB |
| spellingShingle | Miriam Annika Vogt Dragos eInta Alessia eLuoni Hasan eElkin Natascha ePfeiffer Marco Andrea Riva Peter eGass Inducible forebrain-specific ablation of the transcription factor Creb during adulthood induces anxiety but no spatial/contextual learning deficits Frontiers in Behavioral Neuroscience Anxiety Learning Memory BDNF Mouse CREB |
| title | Inducible forebrain-specific ablation of the transcription factor Creb during adulthood induces anxiety but no spatial/contextual learning deficits |
| title_full | Inducible forebrain-specific ablation of the transcription factor Creb during adulthood induces anxiety but no spatial/contextual learning deficits |
| title_fullStr | Inducible forebrain-specific ablation of the transcription factor Creb during adulthood induces anxiety but no spatial/contextual learning deficits |
| title_full_unstemmed | Inducible forebrain-specific ablation of the transcription factor Creb during adulthood induces anxiety but no spatial/contextual learning deficits |
| title_short | Inducible forebrain-specific ablation of the transcription factor Creb during adulthood induces anxiety but no spatial/contextual learning deficits |
| title_sort | inducible forebrain specific ablation of the transcription factor creb during adulthood induces anxiety but no spatial contextual learning deficits |
| topic | Anxiety Learning Memory BDNF Mouse CREB |
| url | http://journal.frontiersin.org/Journal/10.3389/fnbeh.2014.00407/full |
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