ArticleLearning & memory (Cold Spring Harbor, N.Y.)
Chronically increased Gsalpha signaling disrupts associative and spatial learning.
Article in Learning & memory (Cold Spring Harbor, N.Y.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
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- Case Report: Severe McCune-Albright syndrome presenting with neonatal Cushing syndrome: navigating through clinical obstacles.Frontiers in endocrinology · 2023Article
- Brain and eye involvement in McCune-Albright Syndrome: clinical and translational insights.Frontiers in endocrinology · 2023Review
- Article
- Genetically encoded sensors towards imaging cAMP and PKA activity in vivo.Journal of neuroscience methods · 2021Review
- PET Imaging of Phosphodiesterase-4 Identifies Affected Dysplastic Bone in McCune-Albright Syndrome, a Genetic Mosaic Disorder.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2020Article
- Cognitive dysfunction in Huntington's disease: mechanisms and therapeutic strategies beyond BDNF.Brain pathology (Zurich, Switzerland) · 2016Review
- Impaired spatial memory and enhanced long-term potentiation in mice with forebrain-specific ablation of the Stim genes.Frontiers in behavioral neuroscience · 2015Article
- Regulation of neuronal plasticity and fear by a dynamic change in PAR1-G protein coupling in the amygdala.Molecular psychiatry · 2013Article
- miRNA-132: a dynamic regulator of cognitive capacity.Brain structure & function · 2013Article
- McCune-Albright syndrome and the extraskeletal manifestations of fibrous dysplasia.Orphanet journal of rare diseases · 2012Review
- Excess folate during adolescence suppresses thyroid function with permanent deficits in motivation and spatial memory.Genes, brain, and behavior · 2012Article
- Expression profile of rat hippocampal neurons treated with the neuroprotective compound 2,4-dinitrophenol: up-regulation of cAMP signaling genes.Neurotoxicity research · 2010Article
- Cushing syndrome in the McCune-Albright syndrome.The Journal of clinical endocrinology and metabolism · 2010Article
- Developmental etiology for neuroanatomical and cognitive deficits in mice overexpressing Galphas, a G-protein subunit genetically linked to schizophrenia.Molecular psychiatry · 2009Article
- Chronic enhancement of CREB activity in the hippocampus interferes with the retrieval of spatial information.Learning & memory (Cold Spring Harbor, N.Y.) · 2009Article
- A novel conditional genetic system reveals that increasing neuronal cAMP enhances memory and retrieval.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2008Article
- Constitutive activation of the G-protein subunit Galphas within forebrain neurons causes PKA-dependent alterations in fear conditioning and cortical Arc mRNA expression.Learning & memory (Cold Spring Harbor, N.Y.) · 2008Article
- Regulation of hippocampus-dependent memory by cyclic AMP-dependent protein kinase.Progress in brain research · 2008Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The cAMP/PKA pathway plays a critical role in learning and memory systems in animals ranging from mice to Drosophila to Aplysia. Studies of olfactory learning in Drosophila suggest that altered expression of either positive or negative regulators of the cAMP/PKA signaling pathway beyond a certain optimum range may be deleterious. Here we provide genetic evidence of the behavioral and physiological effects of increased signaling through the cAMP/PKA pathway in mice. We have generated transgenic mice in which the expression of a constitutively active form of Gsalpha (Gsalpha* Q227L), the G protein that stimulates adenylyl cyclase activity, is driven in neurons within the forebrain by the promoter from the CaMKIIalpha gene. Despite significantly increased adenylyl cyclase activity, Gsalpha* transgenic mice exhibit PKA-dependent decreases in levels of cAMP due to a compensatory up-regulation in phosphodiesterase activity. Interestingly, Gsalpha* transgenic mice also exhibit enhanced basal synaptic transmission. Consistent with a role for the cAMP/PKA pathway in learning and memory, Gsalpha* transgenic mice show impairments in spatial learning in the Morris water maze and in contextual and cued fear conditioning tasks. The learning deficits observed in these transgenic mice suggest that associative and spatial learning requires regulated Gsalpha protein signaling, much as does olfactory learning in Drosophila.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.