Ca2+-Stimulated Adenylyl Cyclases Regulate ERK-Dependent Activation of MSK1 during Fear Conditioning

Sindreu, Carlos; Scheiner, Zachary S.; Storm, Daniel R.

doi:10.1016/j.neuron.2006.11.024

Cited by 174 publications

(189 citation statements)

References 37 publications

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“…To provide subcellular localization and confirmation of synaptosomal fractionation results, immunohistochemical co-localization of AC1 or AC8 was performed with protein markers and methods that have been successfully utilized to distinguish pre-and postsynaptic sites (Serpinskaya et al, 1999,Fukaya and Watanabe, 2000,Lachamp et al, 2005,Sindreu et al, 2007. Co-expression of AC1 and PSD-95 was observed within multiple structures of the hippocampus (Fig.…”

Section: Resultsmentioning

confidence: 99%

Distinct regional and subcellular localization of adenylyl cyclases type 1 and 8 in mouse brain

et al. 2007

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Adenylyl cyclases (ACs) convert ATP to cAMP and therefore, subserve multiple regulatory functions in the nervous system. AC1 and AC8 are the only cyclases stimulated by calcium and calmodulin, making them uniquely poised to regulate neuronal development and neuronal processes such as learning and memory. Here, we detail the production and application of a novel antibody against mouse AC1. Along with AC8 immunohistochemistry, these data reveal distinct and partially overlapping patterns of protein expression in brain during development and adulthood. AC1 protein increased in abundance in the neonatal hippocampus from postnatal day 7 to 14. By adulthood, abundant AC1 protein expression was observed in the mossy fiber tract in the hippocampus and the molecular layer in the cerebellum, with diffuse expression in the cortex and thalamus. AC8 protein levels were abundant during development, with diffuse and increasing expression in the hippocampus that intensified in the CA1/CA2 region by adulthood. AC8 expression was weak in the cerebellum at postnatal day 7 and decreased further by postnatal day 14. Analysis of synaptosome fractions from the adult brain demonstrated robust expression of AC1 in the postsynaptic density and extrasynaptic regions, while expression of AC8 was observed in the presynaptic active zone and extrasynaptic fractions. These findings were confirmed with localization of AC1 and/or AC8 with PSD-95, Tau, synaptophysin and MAP-2 expression throughout the brain. Together, these data provide insight into the functional roles of AC1 and AC8 as reflected by their distinct localization in cellular and subcellular compartments. Keywords cAMP; presynaptic; synaptosome; calcium; calmodulin The ability of the brain to respond and process information dynamically is dependent on intercellular and intracellular neuronal signaling. Adenylyl cyclases (ACs), which generate cAMP, are critical to the integration of this signaling and are essential to processes such as

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Section: Resultsmentioning

confidence: 99%

Distinct regional and subcellular localization of adenylyl cyclases type 1 and 8 in mouse brain

et al. 2007

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“…To determine PKA activity, we assessed phosphorylated PKA substrate (pPKA-s) levels. Changes in pPKA-s immunoreactivity are reported to be a reliable and sensitive measure of altered PKA activity (26). As is shown in Fig.…”

Section: Unilateral Glucocorticoid Administration Into the Mpfc Does Notmentioning

confidence: 90%

Glucocorticoids in the prefrontal cortex enhance memory consolidation and impair working memory by a common neural mechanism

Barsegyan

Mackenzie

Kurose

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

234

169

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It is well established that acute administration of adrenocortical hormones enhances the consolidation of memories of emotional experiences and, concurrently, impairs working memory. These different glucocorticoid effects on these two memory functions have generally been considered to be independently regulated processes. Here we report that a glucocorticoid receptor agonist administered into the medial prefrontal cortex (mPFC) of male Sprague-Dawley rats both enhances memory consolidation and impairs working memory. Both memory effects are mediated by activation of a membrane-bound steroid receptor and depend on noradrenergic activity within the mPFC to increase levels of cAMPdependent protein kinase. These findings provide direct evidence that glucocorticoid effects on both memory consolidation and working memory share a common neural influence within the mPFC.

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“…Recent studies have shown that MSK1 is activated during contextual fear conditioning (Sindreu et al 2007) and that MSK1 Cold Spring Harbor Laboratory Press on April 6, 2019 -Published by learnmem.cshlp.org Downloaded from deletion impairs fear conditioning as well as spatial memory (Chwang et al 2007). MSK1 2/2 mice have a deficiency in hippocampal histone H3 phosphorylation and acetylation (Chwang et al 2007) and CREB-dependent transcription (Wiggin et al 2002), three events that are linked to both dendritic plasticity and memory (Hsieh and Gage 2005;Levenson and Sweatt 2005).…”

Section: Msk Learning and Memorymentioning

confidence: 99%

MSK1 regulates environmental enrichment-induced hippocampal plasticity and cognitive enhancement

et al. 2012

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Environmental enrichment (EE) has marked beneficial effects on cognitive capacity. Given the possibility that this form of neuronal plasticity could function via the actuation of the same cellular signaling pathways that underlie learning/memory formation, we examined whether the MAPK cascade effector, mitogen/stress-activated kinase 1 (MSK1), could play a role in this process. MSK1 functions as a key signaling intermediate that couples changes in neuronal activity into inducible gene expression, neuronal plasticity, and learning/memory. Here, we show that MSK1 is expressed in excitatory cell layers of the hippocampus, progenitor cells of the subgranular zone (SGZ), and adult-born immature neurons. MSK1 2/2 mice exhibit reduced spinogenesis and decreased dendritic branching complexity in hippocampal neurons, compared with WT mice. Further, in MSK1 2/2 mice, progenitor cell proliferation within the SGZ was significantly reduced and, correspondingly, the number of immature neurons within the dentate gyrus was significantly reduced. Consistent with prior work, MSK1 2/2 mice displayed deficits in both spatial and recognition memory tasks. Strikingly, cognitive enhancement resulting from a 40-d period of EE was markedly reduced in MSK1 2/2 animals. MSK1 2/2 mice exhibited reduced levels of EE-induced spinogenesis and SGZ progenitor proliferation. Taken together, these data reveal that MSK1 serves as a critical regulator of hippocampal physiology and function and that MSK1 serves as a key conduit by which enriching stimuli augment cellular plasticity and cognition.

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Ca2+-Stimulated Adenylyl Cyclases Regulate ERK-Dependent Activation of MSK1 during Fear Conditioning

Cited by 174 publications

References 37 publications

Distinct regional and subcellular localization of adenylyl cyclases type 1 and 8 in mouse brain

Distinct regional and subcellular localization of adenylyl cyclases type 1 and 8 in mouse brain

Glucocorticoids in the prefrontal cortex enhance memory consolidation and impair working memory by a common neural mechanism

MSK1 regulates environmental enrichment-induced hippocampal plasticity and cognitive enhancement

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