Journal article
Chronically increased Gsα signaling disrupts associative and spatial learning
Learning & memory (Cold Spring Harbor, N.Y.), Vol.13(6), pp.745-752
11/01/2006
DOI: 10.1101/lm.354106
PMCID: PMC1783628
PMID: 17142304
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 Gsα (Gsα* Q227L), the G protein that stimulates adenylyl cyclase activity, is driven in neurons within the forebrain by the promoter from the CaMKIIα gene. Despite significantly increased adenylyl cyclase activity, Gsα* transgenic mice exhibit PKA-dependent decreases in levels of cAMP due to a compensatory up-regulation in phosphodiesterase activity. Interestingly, Gsα* transgenic mice also exhibit enhanced basal synaptic transmission. Consistent with a role for the cAMP/PKA pathway in learning and memory, Gsα* 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 Gsα protein signaling, much as does olfactory learning in Drosophila.
Details
- Title: Subtitle
- Chronically increased Gsα signaling disrupts associative and spatial learning
- Creators
- Rusiko BourtchouladzeSusan L PattersonMichele P KellyArati KreibichEric R KandelTed Abel
- Resource Type
- Journal article
- Publication Details
- Learning & memory (Cold Spring Harbor, N.Y.), Vol.13(6), pp.745-752
- DOI
- 10.1101/lm.354106
- PMID
- 17142304
- PMCID
- PMC1783628
- ISSN
- 1072-0502
- eISSN
- 1549-5485
- Language
- English
- Date published
- 11/01/2006
- Academic Unit
- Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
- Record Identifier
- 9984071749502771
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