Emotional stress increases GluA2 expression and potentiates fear memory via adenylyl cyclase 5
Summary: Stress can alter behavior and contributes to psychiatric disorders by regulating the expression of the GluA2 AMPA receptor subunit. We have previously shown in mice that exposure to predator odor stress elevates GluA2 transcription in cerebellar molecular layer interneurons (MLIs), and MLI...
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| Language: | English |
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Elsevier
2025-01-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724015316 |
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| author | Qian Yang Ahmad Abdulla Muhammad Farooq Yoshihiro Ishikawa Siqiong June Liu |
| author_facet | Qian Yang Ahmad Abdulla Muhammad Farooq Yoshihiro Ishikawa Siqiong June Liu |
| author_sort | Qian Yang |
| collection | DOAJ |
| description | Summary: Stress can alter behavior and contributes to psychiatric disorders by regulating the expression of the GluA2 AMPA receptor subunit. We have previously shown in mice that exposure to predator odor stress elevates GluA2 transcription in cerebellar molecular layer interneurons (MLIs), and MLI activity is required for fear memory consolidation. Here, we identified the critical involvement of adenylyl cyclase 5, in both the stress-induced increase in GluA2 in MLIs and the enhancement of fear memory. We found that noradrenaline release during predator odor stress activates AC5 and downstream PKA-CREB signaling. This pathway interacts synergistically with α1-adrenergic receptors to promote synaptic GluA2 expression in MLIs. At a behavioral level, predator odor stress potentiates associative fear memory, and this is abolished in AC5 knockout mice, suggesting that AC5-dependent plasticity is required for enhanced memory formation. Therefore, AC5 is a promising pharmacological target for preventing stress-enhanced fear memory. |
| format | Article |
| id | doaj-art-9a33fb6149ee4a60b5e7688e13e2e22a |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-9a33fb6149ee4a60b5e7688e13e2e22a2025-01-09T06:13:50ZengElsevierCell Reports2211-12472025-01-01441115180Emotional stress increases GluA2 expression and potentiates fear memory via adenylyl cyclase 5Qian Yang0Ahmad Abdulla1Muhammad Farooq2Yoshihiro Ishikawa3Siqiong June Liu4Department of Cell Biology and Anatomy, LSUHSC, New Orleans, LA 70112, USADepartment of Cell Biology and Anatomy, LSUHSC, New Orleans, LA 70112, USA; Southeast Louisiana VA Healthcare System, New Orleans, LA 70119, USADepartment of Cell Biology and Anatomy, LSUHSC, New Orleans, LA 70112, USA; Southeast Louisiana VA Healthcare System, New Orleans, LA 70119, USACardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama, JapanDepartment of Cell Biology and Anatomy, LSUHSC, New Orleans, LA 70112, USA; Southeast Louisiana VA Healthcare System, New Orleans, LA 70119, USA; Corresponding authorSummary: Stress can alter behavior and contributes to psychiatric disorders by regulating the expression of the GluA2 AMPA receptor subunit. We have previously shown in mice that exposure to predator odor stress elevates GluA2 transcription in cerebellar molecular layer interneurons (MLIs), and MLI activity is required for fear memory consolidation. Here, we identified the critical involvement of adenylyl cyclase 5, in both the stress-induced increase in GluA2 in MLIs and the enhancement of fear memory. We found that noradrenaline release during predator odor stress activates AC5 and downstream PKA-CREB signaling. This pathway interacts synergistically with α1-adrenergic receptors to promote synaptic GluA2 expression in MLIs. At a behavioral level, predator odor stress potentiates associative fear memory, and this is abolished in AC5 knockout mice, suggesting that AC5-dependent plasticity is required for enhanced memory formation. Therefore, AC5 is a promising pharmacological target for preventing stress-enhanced fear memory.http://www.sciencedirect.com/science/article/pii/S2211124724015316CP: Neuroscience |
| spellingShingle | Qian Yang Ahmad Abdulla Muhammad Farooq Yoshihiro Ishikawa Siqiong June Liu Emotional stress increases GluA2 expression and potentiates fear memory via adenylyl cyclase 5 Cell Reports CP: Neuroscience |
| title | Emotional stress increases GluA2 expression and potentiates fear memory via adenylyl cyclase 5 |
| title_full | Emotional stress increases GluA2 expression and potentiates fear memory via adenylyl cyclase 5 |
| title_fullStr | Emotional stress increases GluA2 expression and potentiates fear memory via adenylyl cyclase 5 |
| title_full_unstemmed | Emotional stress increases GluA2 expression and potentiates fear memory via adenylyl cyclase 5 |
| title_short | Emotional stress increases GluA2 expression and potentiates fear memory via adenylyl cyclase 5 |
| title_sort | emotional stress increases glua2 expression and potentiates fear memory via adenylyl cyclase 5 |
| topic | CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724015316 |
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