A Novel Conditional Genetic System Reveals That Increasing Neuronal cAMP Enhances Memory and Retrieval

Isiegas, Carolina; McDonough, Conor B.; Huang, Ted; Havekes, Robbert; Fabian, Sara A.; Wu, Long Jun; Xu, Hui; Zhao, Ming; Kim, Jae‐Ick; Lee, Yong Seok; Lee, Hye Ryeon; Ko, Hyoung‐Gon; Lee, Nuribalhae; Choi, Sun Lim; Lee, Jeong Sik; Son, Hyeon; Zhuo, Min; Kaang, Bong Kiun; Abel, Ted

doi:10.1523/jneurosci.2935-07.2008

Cited by 29 publications

(40 citation statements)

References 61 publications

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“…To validate the virally induced octopamine receptor expression, we used a separate set of mice to collect perfusion-fixed brains for immunohistohemical analysis. Transcardial perfusions and immunohistochemistry were conducted as described previously van der Borght et al, 2007;Isiegas et al, 2008). To detect DmOct␤1R-HA, we used a monoclonal antibody directed against the HA tag (Roche), biotinylated goat anti-rabbit secondary antibody (1:500; Jackson ImmunoResearch), and avidin-biotin-horseradish peroxidase complex (1: 500; ABC Kit; Vector Laboratories).…”

Section: Methodsmentioning

confidence: 99%

Transiently Increasing cAMP Levels Selectively in Hippocampal Excitatory Neurons during Sleep Deprivation Prevents Memory Deficits Caused by Sleep Loss

et al. 2014

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The hippocampus is particularly sensitive to sleep loss. Although previous work has indicated that sleep deprivation impairs hippocampal cAMP signaling, it remains to be determined whether the cognitive deficits associated with sleep deprivation are caused by attenuated cAMP signaling in the hippocampus. Further, it is unclear which cell types are responsible for the memory impairments associated with sleep deprivation. Transgenic approaches lack the spatial resolution to manipulate specific signaling pathways selectively in the hippocampus, while pharmacological strategies are limited in terms of cell-type specificity. Therefore, we used a pharmacogenetic approach based on a virus-mediated expression of a G␣s-coupled Drosophila octopamine receptor selectively in mouse hippocampal excitatory neurons in vivo. With this approach, a systemic injection with the receptor ligand octopamine leads to increased cAMP levels in this specific set of hippocampal neurons. We assessed whether transiently increasing cAMP levels during sleep deprivation prevents memory consolidation deficits associated with sleep loss in an object-location task. Five hours of total sleep deprivation directly following training impaired the formation of object-location memories. Transiently increasing cAMP levels in hippocampal neurons during the course of sleep deprivation prevented these memory consolidation deficits. These findings demonstrate that attenuated cAMP signaling in hippocampal excitatory neurons is a critical component underlying the memory deficits in hippocampus-dependent learning tasks associated with sleep deprivation.

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Section: Methodsmentioning

confidence: 99%

Transiently Increasing cAMP Levels Selectively in Hippocampal Excitatory Neurons during Sleep Deprivation Prevents Memory Deficits Caused by Sleep Loss

et al. 2014

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“…Coronal sections were cut at a thickness of 30 mm and collected in PBS containing 0.02% sodium azide and stored at 48C until further processing. The procedure used for immunohistochemistry was executed as described previously (Havekes et al 2006;Isiegas et al 2008). Floating sections were washed with PBS (5 min), incubated with 0.1% H 2 O 2 in PBS (30 min) followed by rinsing in PBS (3 times, 5 min).…”

Section: Immunohistochemistrymentioning

confidence: 99%

Subregion-specific p300 conditional knock-out mice exhibit long-term memory impairments

Oliveira¹,

Estévez²,

Hawk³

et al. 2011

Learn. Mem.

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Histone acetylation plays a critical role during long-term memory formation. Several studies have demonstrated that the histone acetyltransferase (HAT) CBP is required during long-term memory formation, but the involvement of other HAT proteins has not been extensively investigated. The HATs CBP and p300 have at least 400 described interacting proteins including transcription factors known to play a role in long-term memory formation. Thus, CBP and p300 constitute likely candidates for transcriptional coactivators in memory formation. In this study, we took a loss-of-function approach to evaluate the role of p300 in long-term memory formation. We used conditional knock-out mice in which the deletion of p300 is restricted to the postnatal phase and to subregions of the forebrain. We found that p300 is required for the formation of long-term recognition memory and long-term contextual fear memory in the CA1 area of the hippocampus and cortical areas.

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“…Further, activation of at least two targets of cAMP signaling, protein kinase A (PKA) and the exchange protein activated by cAMP (Epac), is also required for hippocampus-dependent memory retrieval. Finally, transgenic mice expressing an invertebrate, G s -coupled octopamine receptor exhibit both octopamine-dependent increases in DH cAMP and enhanced contextual fear memory retrieval (Isiegas et al 2008).…”

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confidence: 99%

Xamoterol impairs hippocampus-dependent emotional memory retrieval via G_i/o-coupled β₂-adrenergic signaling

Schutsky¹,

Ouyang²,

Thomas³

2011

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Xamoterol, a partial b 1 -adrenergic receptor agonist, has been reported to impair the retrieval of hippocampus-dependent spatial reference memory in rats. In contrast, xamoterol restores memory retrieval in gene-targeted mice lacking norepinephrine (NE) and in a transgenic mouse model of Down syndrome in which NE levels are reduced. Restoration of retrieval by xamoterol in these two models complements the observation that NE and b 1 signaling are required for hippocampusdependent retrieval of contextual and spatial reference memory in wild-type mice and rats. Additional evidence indicates that cAMP-mediated PKA and Epac signaling are required for the retrieval of hippocampus-dependent memory. As a result, we hypothesized that xamoterol has effects in addition to the stimulation of b 1 receptors that, at higher doses, act to counter the effects of b 1 signaling. Here we report that xamoterol-induced disruption of memory retrieval depends on b 2 -adrenergic receptor signaling. Interestingly, the impairment of memory retrieval by xamoterol is blocked by pretreatment with pertussis toxin, an uncoupling agent for G i/o signaling, suggesting that b 2 signaling opposes b 1 signaling during memory retrieval at the level of G protein and cAMP signaling. Finally, similar to the time-dependent roles for NE, b 1 , and cAMP signaling in hippocampus-dependent memory retrieval, xamoterol only impairs retrieval for several days after training, indicating that its effects are also limited by the age of the memory. We conclude that the disruption of memory retrieval by xamoterol is mediated by G i/o -coupled b 2 signaling, which opposes the G s -coupled b 1 signaling that is transiently required for hippocampus-dependent emotional memory retrieval.

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A Novel Conditional Genetic System Reveals That Increasing Neuronal cAMP Enhances Memory and Retrieval

Cited by 29 publications

References 61 publications

Transiently Increasing cAMP Levels Selectively in Hippocampal Excitatory Neurons during Sleep Deprivation Prevents Memory Deficits Caused by Sleep Loss

Transiently Increasing cAMP Levels Selectively in Hippocampal Excitatory Neurons during Sleep Deprivation Prevents Memory Deficits Caused by Sleep Loss

Subregion-specific p300 conditional knock-out mice exhibit long-term memory impairments

Xamoterol impairs hippocampus-dependent emotional memory retrieval via G_i/o-coupled β₂-adrenergic signaling

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A Novel Conditional Genetic System Reveals That Increasing Neuronal cAMP Enhances Memory and Retrieval

Cited by 29 publications

References 61 publications

Transiently Increasing cAMP Levels Selectively in Hippocampal Excitatory Neurons during Sleep Deprivation Prevents Memory Deficits Caused by Sleep Loss

Transiently Increasing cAMP Levels Selectively in Hippocampal Excitatory Neurons during Sleep Deprivation Prevents Memory Deficits Caused by Sleep Loss

Subregion-specific p300 conditional knock-out mice exhibit long-term memory impairments

Xamoterol impairs hippocampus-dependent emotional memory retrieval via Gi/o-coupled β2-adrenergic signaling

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Xamoterol impairs hippocampus-dependent emotional memory retrieval via G_i/o-coupled β₂-adrenergic signaling